Nicotine exposure in breastfed infants.

AIM: To study exposure to nicotine in breastfed infants in relation to parental smoking habits. MATERIAL AND METHODS: Forty mother-infant pairs were studied. Twenty non-smoking mothers, 18 smoking (2-20 cigarettes per day) and two snuff-taking mothers were included. All infants were healthy, exclusively breastfed and their postnatal age was 6 wk. During a home visit, parental smoking habits were recorded, and the time of mothers' last smoke or taking of snuff and breastfeeding were recorded. Breast milk and infant urine samples were collected. Concentrations of nicotine and cotinine were analysed with gas chromatography. The amount of milk ingested during the home visit was calculated by weighing the infants. RESULTS: Two non-smoking and non-snuff-taking women had milk containing nicotine (28 and 13 microg/l, respectively). Both had smoking spouses. In the smoking and snuff-taking group, the mean (SD) milk nicotine concentration was 44 (38) microg/l (n = 36). When milk samples taken 7 h and 0.6 h after smoking were compared, the concentration of milk nicotine increased from 21 to 51 microg/l (p < 0.01). The two snuff-taking mothers exposed their children to higher milk nicotine concentrations than all but two of the smokers. The concentrations of the metabolite cotinine in infant urine correlated with the dose of nicotine ingested during the home visit (r = 0.84, p < 0.01). CONCLUSIONS: Breastfed infants with a smoking or snuff-taking mother are exposed to nicotine in breast milk. The mean intake of nicotine via milk is 7 microg/kg/d. With a shorter time between the mothers' smoking and breastfeeding, the milk nicotine concentration will increase. Both passive smoking at home and snuff-taking were associated with measurable nicotine levels in milk. Healthcare personnel promoting breastfeeding should be aware of these factors influencing exposure to nicotine in the breastfed infant.

Hospital-managed advanced care of children in their homes.

A hospital-managed project for the advanced care of children in their homes (SABH) has been established in Sweden. The aim was to provide an alternative to inpatient paediatric care by providing hospital-at-home care to stable infants and children using mobile units based on advanced information and communication technology. The Karolinska Hospital children's ward and emergency room referred children to SABH care. A medical care plan was drawn up by the physicians and nurses responsible for the patient while in hospital, in conjunction with the parents and the patient. In one year, 350 episodes of care requiring 3000 bed-days were managed by SABH in the children's homes rather than at hospital. Forty-two per cent of the patients were aged less than one year, 41% were between one and six years old, and 17% were older than six years. SABH care was at least 30% cheaper than conventional hospital care and patient satisfaction with the service was high. At the conclusion of the two-year project, the SABH became a permanent unit at the Karolinska Hospital.

[Rheumatic fever behind acute chorea in a young girl. A case report]. / Reumatisk feber bakom hastigt påkommen korea hos ung flicka. En fallbeskrivning.

This article presents the case of a 13-year old girl who was admitted to the emergency department because of rapidly evolving, seriously disabling impairments in movement and speech. Investigation led to the conclusion that her problems were caused by Sydenham's chorea as a manifestation of rheumatic fever. A neuropsychiatric examination performed one year after the onset of disease revealed a hitherto unknown mild mental retardation. The case description is followed by a clinical update on rheumatic fever focusing on cerebral manifestations. The theories concerning the existence of PANDAS--an autoimmune neuropsychiatric disorder following streptococcal infections, distinct from rheumatic fever--are presented.

The outcome of children born with pulmonary atresia and intact ventricular septum in Sweden from 1980 to 1999.

OBJECTIVE: To study the outcome of all children born with pulmonary atresia and intact ventricular septum in Sweden between 1980 and 1999. DESIGN: Retrospective study of medical records with review of the initial, preoperative angiocardiographic and echocardiographic examinations. RESULTS: A total of 84 children were born with pulmonary atresia and intact ventricular septum, giving an incidence of 4.2 per 100,000 live births. In all, 77 were operated on with a 1-year survival rate of 75%. Thirty-six children had ventriculocoronary communications, with a 1-year survival rate of 50%. At the end of the study period, 52 children were alive, 32 with biventricular repair, and 19 with univentricular repair. Follow-up time was 14 days-20 years (median, 6 years). Statistical analysis of incremental risk factors for death showed statistical significance for low birth weight, male sex, muscular pulmonary atresia, and having a systemic-to-pulmonary shunt as the sole initial intervention. CONCLUSION: Complete national data of all patients born with pulmonary atresia and intact ventricular septum during 1980-1999 in Sweden revealed a total mortality in accordance with previous reports for results for surgery. Further improvements demand a thorough preoperative investigation of the cardiac anatomy, particularly of the ventriculocoronary communications, to enable right ventricular decompression whenever possible.

Magnetic resonance imaging and echocardiography in assessment of ventricular function in atrially corrected transposition of the great arteries.

OBJECTIVE: Patients with atrial correction of transposition of the great arteries (TGA) may develop right ventricular (RV) failure with time. A reliable non-invasive method for assessment of ventricular function is therefore needed. To evaluate the accuracy of echocardiography in assessment of ventricular volumes and function in these patients we compared echocardiography with magnetic resonance imaging (MRI) in 10 patients late after the Mustard and Senning procedures. DESIGN: Prospective echocardiography and MRI examinations were performed on the same day. Two different echocardiography technicians examined all patients. All echocardiography and MRI examinations were performed at the university hospital outpatient clinic and MRI department respectively. Ten patients, age 14.0+/-2.9 years, who had been operated on with atrial correction of TGA at 8 (2-60) months of age (median and range) were examined. Echocardiography RV and left ventricular (LV) end-systolic volumes (ESVs), end-diastolic volumes (EDVs), stroke volumes (SVs) and ejection fractions (EFs) were calculated, using the modified Simpson method, and compared with the same measurements obtained from MRI. RESULTS: For RV function there was good agreement between echocardiography- and MRI-derived measurements. Both echocardiography and MRI revealed reduced RV function with EFs of 42.6+/-9.1% and 46.4+/-7.2% respectively. For RV volumes there were no significant differences between echocardiography and MRI. LV function was significantly overestimated by echocardiography (EF with echocardiography = 72.7+/-4.4% vs. MRI = 50.5+/-7.6%) while all LV volumes were greatly underestimated. Echocardiography measurements of volumes in repeated examinations by different technicians showed large variations, 13-50%, for different variables in individual patients. CONCLUSION: Echocardiography can provide clinically important information concerning RV function in follow-up of patients late after atrial correction of TGA. It has limited value in assessment of LV function in these patients. Volume measurements by echocardiography are, however, highly user-dependent and interobserver variation is high. MRI may accordingly serve as an important reference method in individual patients.

WHIPS--Volvo's Whiplash Protection Study.

Whiplash associated disorders (WAD) resulting from rear end car impacts are an increasing problem. WAD are usually not life threatening, but are one of the most important injury categories with regard to long-term consequences. This paper is a review of Volvo's Whiplash Protection Study (WHIPS), which is the result of more than ten years of concentrated research efforts in the area of neck injuries in car collisions, with the focus on rear end car impacts. The study follows the whole chain from accident research to the development of a seat for increased protection against WAD. Results from Volvo's accident research are summarized. Existing biomechanical knowledge regarding possible injury mechanisms are presented and discussed. Based on the interpretation of accident research and biomechanical knowledge, guidelines for improved protection against WAD in rear end impacts are presented. Requirements and test methods based on the guidelines are explained. An important part of the study is a new rear end impact dummy, BioRID. Test results using the new dummy are presented. Finally, the paper explains the design of a new seat for increased WAD protection, the WHIPS-seat. Results from the accident research and biomechanical research emphasize the importance of considering the whole spine of the occupant and, accordingly, the whole seat when addressing WAD in rear end impacts, with a particular focus on low and moderate impact severity. Low and moderate impact severity crashes should be focused. Also important to consider are the individual differences between occupants, the seating position and the variety of seating postures. All results, including sub-system testing, mathematical modeling, sled testing, as well as geometrical parameters show that the WHIPS-seat will have considerable potential for offering increased protection against WAD in rear end impacts.

Mortality in Down's syndrome in relation to congenital malformations.

Down's syndrome (DS) is the most common form of intellectual disability. The syndrome is characterized by congenital malformations, especially of the heart and gastrointestinal tract, which can result in high mortality rates in the affected population. Many improvements have been made in the medical treatment of this syndrome during the past few decades and the survival of individuals with DS has increased in the industrial world. The aim of the present study was to investigate mortality in relation to congenital malformations. Medical records from all liveborn children with DS delivered between 1973 and 1980 in northern Sweden were studied, and malformations and causes of death were recorded. Out of the 219 children included in the study, a congenital heart defect was reported in 47.5% of subjects, 42.1% of whom had complete atrioventricular septal defect. Gastrointestinal tract malformations were present in 7.3% of subjects, and was frequently associated with a cardiac malformation and a very high mortality rate. Other major and minor congenital anomalies were present in 5.5% and 5.5% of subjects, respectively. In the 14.5-year follow-up of 213 children, the rate of survival was 75.6%. Mortality rates within one and 10 years after birth were 14.6% and 23.5%, respectively. Mortality within 10 years differed significantly between children with (44.1%) and without (4.5%) a congenital heart defect. A very high mortality rate was observed among children with a congenital heart defect, especially when it was combined with a gastrointestinal malformation.

Clinical scale expansion of cryopreserved small volume whole bone marrow aspirates produces sufficient cells for clinical use.

Ex vivo expansion of bone marrow (BM) mononuclear cells (MNC) in a perfused culture system produces stem-progenitor cell type(s) in sufficient number(s) for hematopoietic reconstitution. The limitations in using fresh BM MNC for ex vivo expansion include additional cell processing and inflexibility in patient treatment. Cryopreservation of whole bone marrow (WBM) eliminates processing costs of MNC or CD34+ cell selection and allows for flexibility in patient treatment. We developed a convenient system to cryopreserve and thaw small volume WBM aspirations (n = 13) and then compared the expandability of unprocessed normal cryopreserved/thawed (C/T) WBM to that of fresh BM MNC cultured in the presence of erythropoietin, PIXY 321, and Flt3-ligand. Ex vivo expansion potential was retained in WBM aspirates after C/T. When initiated with 225 million viable nucleated cells, clinical scale expansion cultures (n = 6) yielded 9.7+/-2.8 x 10(8) total cells, which contained 10.4+/-5.8 x 10(6) colony-forming units-granulocyte-macrophage (CFU-GM), 1.3+/-1.4 x 10(4) LTCIC, and 2.2 x 10(6) CD34+Lin- cells, sufficient cell numbers for clinical use. These studies demonstrate that ex vivo perfusion culture expansion of unfractionated C/T WBM (< or =30 ml) provides doses of stem-progenitor cells similar in composition to expanded fresh BM MNC, previously demonstrated to achieve hematopoietic reconstitution.

Ex vivo expansion of bone marrow from breast cancer patients: reduction in tumor cell content through passive purging.

High-dose chemotherapy (HDC) with hematopoietic support appears promising in the treatment of breast cancer, although reinfusion of contaminating tumor cells may contribute to disease relapse. Ex vivo expansion may reduce tumor cell content through use of a small inoculum volume and by passive purging during culture. We assessed the ex vivo expansion potential of tumor cell positive bone marrow (BM) from breast cancer patients and the effect of ex vivo expansion on tumor cell content. Cryopreserved/thawed mononuclear cell (C/T MNC) BM harvests with known tumor cell contamination (n = 7) were assessed for tumor cells pre- and post-expansion using immunocytochemical (ICC) staining. Pre-expansion inoculum samples contained a range of 6-2128 tumor cells per 5.0 x 10(6) nucleated cells. Ex vivo expansion resulted in fold expansions of 6.67 and 11.37 for total cells and CFU-GM, respectively. Tumor cells were undetectable in four of the seven post-expansion samples and were reduced in the remaining three samples. The data demonstrate passive purging of breast cancer cells during ex vivo expansion, with hematopoietic progenitor cell expansion comparable to that of normal BM. Reduction in tumor cell number contained in the small volume culture inoculum combined with passive purging during the ex vivo expansion process suggest a potential 2-4+ log reduction in tumor cell content in the reinfused cell product.

Activation of beta1 integrins on CML progenitors reveals cooperation between beta1 integrins and CD44 in the regulation of adhesion and proliferation.

Adhesion of normal colony-forming cells (CFC) to bone marrow (BM) stroma and the extracellular matrix (ECM) component fibronectin (FN) depends at least in part on the alpha4beta1 and alpha5beta1 integrins and the CD44 receptor. Aside from anchoring progenitors in the marrow microenvironment, beta1 integrin-dependent adhesion of normal CFC is associated with inhibition of their proliferation. In contrast to normal CFC, chronic myelogenous leukemia (CML) Ph+ CFC adhere significantly less to either stroma or FN. CML Ph+ CFC proliferation is also not inhibited by coculture with stroma or FN. However, equal numbers of alpha4, alpha5, and beta1 integrins and CD44 are present on CML and normal CD34+ cells. We have previously demonstrated that beta1-dependent adhesion to and subsequent proliferation inhibition by FN can be restored when CML Ph+ CFC are incubated with the beta1 integrin activating antibody, 8A2, and demonstrated a role for the alpha5beta1 integrin in this phenomenon. Since the integrin alpha4beta1 and the proteoglycan form of CD44 may cooperate in establishing normal CFC adhesion to FN, we examined if treatment of CML Ph+ CFC with 8A2 also restores the cooperativity between beta1 integrins and CD44. We demonstrate that 8A2 induces adhesion of CML Ph+ CFC not only to intact FN but also to alpha4beta1, alpha5beta1, and proteoglycan binding fragments of FN. 8A2-induced adhesion to these fragments and peptides also results in a significant inhibition of the proliferation of CML Ph+ CFC. Addition of antibodies to either the alpha5, alpha4, or beta1 integrins, antibodies against the CD44 receptor, or removal of chondroitin sulfate glycosaminoglycans from the surface of CML CD34+ HLA-DR+ cells significantly reduced the 8A2-induced adhesion to and adhesion-mediated inhibition of proliferation by FN. These studies demonstrate that activation of beta1 integrins on CML Ph+ CFC not only results in upregulation of beta1 integrin-dependent adhesion and adhesion-mediated inhibition of proliferation, but also in the restoration of cooperation between beta1 integrins and CD44. These studies suggest that decreased beta1 integrin avidity may also affect the function of the proteoglycan adhesion receptor CD44, both of which may contribute to the abnormal circulation and expansion of malignant progenitors in CML.

Integrin-mediated regulation of hematopoiesis: do BCR/ABL-induced defects in integrin function underlie the abnormal circulation and proliferation of CML progenitors?

Hematopoiesis takes place in close contact with the marrow microenvironment. Normal progenitors adhere through a variety of receptors to stroma and extracellular matrix components, including fibronectin. Adhesion through integrins to fibronectin may not only serve to anchor progenitors to the microenvironment but also to directly alter the proliferative behavior of normal hematopoietic progenitors. Chronic myelogenous leukemia (CML) is a malignant disease of the hematopoietic stem cell. At the molecular level, CML is characterized by the BCR/ABL gene rearrangement which encodes for the oncoprotein, p210bcr-abl. Presence of the p210bcr-abl tyrosine kinase is necessary and sufficient for the malignant transformation of hematopoietic cells. Clinically, CML is characterized by an abnormal, premature release of primitive progenitors and precursors in the blood and by the continuous proliferation of the malignant progenitor population. In vitro, CML progenitors fail to adhere to or be regulated by marrow stroma. Since CML progenitors express similar numbers of integrin adhesion receptors as normal progenitors, functional rather than quantitative differences of these receptors on CML progenitors may be responsible for the abnormal circulation and proliferation of the malignant clone. In this manuscript we will review the role of integrin adhesion receptors present on normal hematopoietic progenitors in the regulation of their proliferation and discuss signal transduction mechanisms that may be responsible for these effects. We will also discuss the integrin defect in CML which may be caused by the presence of the oncoprotein, P210bcr-abl, and may explain the abnormal trafficking and proliferation observed in CML.

Oxygen consumption in infants and children during heart catheterization.

Oxygen consumption was measured in infants, children, and adolescents during diagnostic heart catheterizations. A total of 825 measurements of oxygen consumption (VO2) was performed in 504 subjects using a semiopen hood system and a paramagnetic oxygen analyzer. In 256 subjects under 3 years of age, body dimensions and heart rate were found to be significant factors for oxygen consumption. The regression equation for both sexes was: VO2/BSA (ml/min.m2) = 3.42.height (cm) - 7.83.weight (kg) + 0.38.HR - 54.1 (r2 = 0.39, SD = 38.7), where BSA is body surface area and HR is heart rate. VO2/BSA was significantly lower in infants less than 3 months of age (133 +/- 33 ml/min.m2) compared with infants of 3-12 months (171 +/- 37 ml/ min.m2; p < 0.01). In 272 children aged 3 years and older and adolescents, gender was a significant factor in oxygen consumption together with BSA and HR. The regression line equation for males was VO2/BSA (ml/ min.m2) = 0.79.HR - 7.4.BSA(m2) + 108.1 (r2 = 0.45, SD = 34.2). The regression line equation for females is VO2/BSA (ml/min.m2) = 0.77.HR - 5.2.BSA(m2) + 106.8 (r2 = 0.43, SD = 34.4). Hematocrit, systemic oxygen saturation, and blood pressure were not significant factors. The predictive value of nomograms for oxygen consumption is limited because of the large interindividual variations not explained by differences in gender, body size, or simple hemodynamic variables. Preferably, oxygen consumption is measured; but if nomograms for oxygen consumption are used for hemodynamic assessment, the wide confidence intervals should be considered.

Activation-dependent alpha5beta1 integrin-mediated adhesion to fibronectin decreases proliferation of chronic myelogenous leukemia progenitors and K562 cells.

Chronic myelogenous leukemia (CML) is a malignant disease of the hematopoietic stem cell characterized by abnormal circulation and proliferation of malignant progenitors. In contrast to their normal counterparts, CML progenitors adhere poorly to bone marrow stroma or fibronectin (FN). Aside from anchoring progenitors in the marrow microenvironment, beta1 integrin-dependent adhesion of normal progenitors is also associated with inhibition of their proliferation. As the beta1 integrin expression on CML progenitors is normal, we hypothesized that decreased integrin affinity may underlie the abnormal adhesive and proliferative characteristics of CML progenitors. We examined the effect of affinity modulation by the activating antibody 8A2 on the adhesion and proliferation of CML progenitors and the CML cell line, K562. 8A2 induced alpha5Beta1-dependent adhesion of Philadelphia chromosome-positive (Ph+) CD34+/HLA-DR+ cells and K562 cells to FN. Increased adhesion was 8A2- and FN concentration-dependent, time-dependent, and energy-dependent. Further, 8A2-induced adhesion to FN significantly inhibited the proliferation of malignant CML progenitors as well as K562 cells independent of cell differentiation, necrosis, or apoptosis. These studies demonstrate that affinity modulation of the alpha5Beta1 integrin on CML progenitors and K562 cells by 8A2 results in increased adhesion to FN with subsequent decreased proliferation, suggesting that decreased beta1 integrin affinity contributes to the abnormal circulation and proliferation of malignant progenitors in CML.

Inhaled nitric oxide in neonates and children with pulmonary hypertension.

Fourteen critically ill neonatal and paediatric intensive care patients with various primary diagnoses and signs of associated pulmonary hypertension received inhaled nitric oxide (NO), 20-80 ppm, after failure of conventional therapy to improve oxygenation. NO administration was found to be associated with a significant improvement in postductal arterial oxygen tension (pre-NO: 3.75 (SD 1.39) kPa; post-NO: 6.05 (SD 1.70) kPa; p = 0.004). In 10 patients, NO was found to increase arterial oxygen tension with more than 1 kPa. In 2 of these patients, ECMO treatment could be avoided due to the pronounced improvement in gas exchange seen after the initiation of NO administration. The remaining 4 patients failed to respond to NO administration. One patient developed methaemoglobinaemia (13.9%) which required treatment with methylthionine. Since we were unable to produce any beneficial effect of NO in the late phase of the pulmonary disease process, we believe that, in order to be successful, inhaled NO should be instituted when conventional treatment has failed and the administration of an iv vasodilator is usually considered.

Effect of inhaled nitric oxide on raised pulmonary vascular resistance in children with congenital heart disease.

OBJECTIVE: To study the short-term effects of inhaled nitric oxide in infants and young children with congenital heart disease. SETTING: A supraregional referral centre for children with congenital heart disease. PATIENTS AND METHODS: 22 infants and children aged 3-32 months (median age 5 months) with congenital heart disease undergoing preoperative cardiac catheterisation. All but one infant had intracardiac shunt lesions and 13 had increased pulmonary vascular resistance. During catheterisation the patients inhaled nitric oxide in a concentration of 40 parts per million in room air. Pulmonary and systemic haemodynamic variables were evaluated by means of measured oxygen consumption and the Fick principle before and after 10 minutes' exposure to nitric oxide. RESULTS: Inhaled nitric oxide did not affect the systemic circulation. There was a significant reduction in the pulmonary vascular resistance, but only in the 13 infants with pulmonary hypertension, in whom pulmonary vascular resistance was reduced by 34% from 8.6 (4.6) mm Hg.min.m2.l-1 (mean (SD)) to 5.7 (3.5) mm Hg.min.m2.l-1. The pulmonary circulation in infants with normal pulmonary vascular resistance was not affected. No statistically significant increase in methaemoglobin was seen, though there were large individual differences. No other side effects were seen. CONCLUSION: The present study shows that in infants with congenital heart disease inhaled nitric oxide reduced pathologically increased pulmonary vascular resistance without affecting systemic circulation and without important side effects with brief exposure.

The neonatal guinea pig as a model for human galactose metabolism: galactose-1-phosphate uridyltransferase activity.

The specific activity of galactose-1-phosphate uridyltransferase was measured in fetal and neonatal guinea pig liver during the first 10 days of age. Activity was approximately six times greater than in adult animals, and peaked during the first 48 h after birth. Activity dropped sharply during the next 2 days, followed by a gradual decline. Liver galactose and glycogen levels were stable throughout the study period. Liver glucose rose significantly after birth, then dropped slightly. The pattern of uridyltransferase in the guinea pig is similar to that reported for phosphoenolpyruvate carboxylkinase and pyruvate carboxylase. Compared to the rat, specific activity of uridyltransferase peaked earlier, possibly due to the guinea pig's advanced maturity.

Postnatal changes in intracranial blood flow velocity in preterm infants.

Postnatal changes in intracranial arterial blood flow velocity, were studied in preterm infants of less than 34 weeks of gestation. The blood flow velocity was measured in an artery on the base of the skull, using a range-gated Doppler ultrasound velocimeter. Ten healthy infants (mean gestational age 32.5 weeks), and ten infants with transitional respiratory disease (mean gestational age 31.3 weeks) were studied at 1, 2, 5, 24 h, and 2, 3, 5 and 10 days after birth. The healthy infants showed a consistent pattern of changes on the first day, with an average reduction in mean flow velocity of 29% between 1 and 5 h. At 24 h after birth, mean flow velocity had almost returned to the level of the 1 h recording. After 24 h there was a gradual increase in systolic and mean flow velocity until 10 days, while diastolic flow velocity remained unchanged. In the infants with respiratory disease there were no systematic changes in mean flow velocity on the first day, although large individual changes were seen. After 24 h no differences were seen between the healthy infants and the infants with respiratory disease. These findings indicate a transient decrease in cerebral perfusion during early circulatory transition in healthy preterm infants, and that mild to moderate respiratory disease causes larger individual variations in intracranial blood flow velocity.

Left ventricular stroke volume and output in healthy term infants.

Left ventricular output, left ventricular stroke volume, and systemic vascular resistance were measured noninvasively in 16 healthy term infants at 6 predefined time intervals from less than 15 minutes to 72 hours after birth. The blood flow velocity in the ascending aorta was measured by range-gated Doppler technique and multiplied by the cross-sectional area, measured by 2-dimensional and M-mode echocardiography to yield left ventricular output. Stroke volume was calculated by dividing left ventricular output by heart rate. Mean arterial blood pressure was measured by oscillometric technique and used for calculation of systemic vascular resistance. A poor association between heart rate and left ventricular output was found, whereas there was a very close relationship between stroke volume and left ventricular output. There was also a reciprocal relationship between systemic vascular resistance and stroke volume. This suggests that stroke volume and not heart rate is the main determinant of neonatal left ventricular output and that the low postnatal afterload might strengthen this relationship.