Anders Jonzon

Supplementary oxygen and risk of childhood lymphatic leukaemia

Aim: Childhood leukaemia has been linked to several factors, such as asphyxia and birthweight, which in turn are related to newborn resuscitation. Based on the findings from a previous study a population‐based case‐control study was performed to investigate the association between childhood leukaemia and exposure to supplementary oxygen and other birth‐related factors. Methods: Children born in Sweden and diagnosed with lymphatic leukaemia between 1973 and 1989 (578 cases) were individually matched by gender and date of birth to a randomly selected control. Children with Downs syndrome were excluded. Exposure data were blindly gathered from antenatal, obstetric and other standardized medical records. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated by conditional logistic regression. Results: Resuscitation with 100% oxygen with a facemask and bag immediately postpartum was significantly associated with an increased risk of childhood lymphatic leukaemia (OR = 2.57, 95% CI 1.21–6.82). The oxygen‐related risk further increased if the manual ventilation lasted for 3 min or more (OR = 3.54, 95% CI 1.16–10.80). Low Apgar scores at 1 and 5 min were associated with a non‐significantly increased risk of lymphatic leukaemia. There were no associations between lymphatic leukaemia and supplementary oxygen later in the neonatal period or other birth‐related factors.

Development of heart block in children of SSA/SSB-autoantibody-positive women is associated with maternal age and displays a season-of-birth pattern

Objective Congenital heart block may develop in the fetuses of Ro/SSA-positive and La/SSB-positive mothers. Recurrence rates of only 10–20% despite persisting maternal antibodies indicate that additional factors are critical for the establishment of heart block. The authors investigated the influence of other maternal and fetal factors on heart block development in a Swedish population-based cohort. Methods The influence of fetal gender, maternal age, parity and time of birth on heart block development was analysed in 145 families, including Ro/La-positive (n=190) and Ro/La-negative (n=165) pregnancies. Results There was a recurrence rate of 12.1% in Ro/La-positive women, and no recurrence in Ro/La-negative women. Fetal gender and parity did not influence the development of heart block in either group. Maternal age in Ro/La-positive pregnancies with a child affected by heart block was, however, significantly higher than in pregnancies resulting in babies without heart block (p<0.05).Seasonal timing of pregnancy influenced the outcome. Gestational susceptibility weeks 18–24 occurring during January–March correlated with a higher proportion of children with heart block and lower vitamin D levels during the same period in a representative sample of Swedish women and a corresponding higher proportion of children with heart block born in the summer (p<0.02). Maternal age or seasonal timing of pregnancy did not affect the outcome in Ro/La-negative pregnancies. Conclusion This study identifies maternal age and seasonal timing of pregnancy as novel risk factors for heart block development in children of Ro/La-positive women. These observations may be useful for counselling when pregnancy is considered.

Long-term survival in children with atrioventricular septal defect and common atrioventricular valvar orifice in Sweden

BACKGROUND The survival for patients with atrioventricular septal defect has improved markedly over the last decades and, during the same period, the survival of children with Downs syndrome has also increased. The aim of our study was to investigate long-term survival in patients having atrioventricular septal defect with common valvar orifice, but without associated significant congenital heart defects, in the setting of Downs syndrome, comparing the findings to those in chromosomally normal children with the same malformation. METHODS AND RESULTS In a population-based retrospective study, we scrutinised the medical records from 801 liveborn children with atrioventricular septal defect born in Sweden during the period 1973 through 1997. Data on gender, presence or absence of Downs syndrome, associated congenital heart defects, date of birth, operation and death were recorded and followed up until 2001. An isolated atrioventricular septal defect with common atrioventricular valvar orifice was present in 502 children, of whom 86% had Downs syndrome. We found a significant reduc tion over time in age at operation, and in postoperative mortality at 30 days, from 28 to 1%. Using a multiple logistic regression model, we found no significant differences in mortality between genders, nor between those with or without Downs syndrome. Early corrective surgery could not be identified as a significant independent factor for survival. The 5-year postoperative survival in patients with Downs syndrome increased from 65% over the period from 1973 through 1977, to about 90% in the period 1993 through 1997, and the same trend was observed in chromosomally normal patients. CONCLUSIONS Survival in uncomplicated atrioventricular septal defect with common atrioventricular valvar orifice has greatly increased, and surgical correction is now equally successful in patients with Downs syndrome and chromosomally normal patients, and for both genders. Death in connection with surgery is no longer the major threat, and focus must now be on long-term follow-up.

A population-based investigation of the autoantibody profile in mothers of children with atrioventricular block.

The objective of the study was to investigate the antigen specificity and occurrence of individual autoantibodies in mothers of children diagnosed with atrioventricular (AV) block in a nation‐wide setting. Patients with AV block detected before 15 years of age were identified using national quality registries as well as a network of pediatric and adult cardiologists and rheumatologists at the six university hospitals in Sweden. Patients with gross heart malformations, surgically or infectiously induced blocks were excluded. Blood samples were obtained from the mothers and maternal autoantibody profile, including the occurrence of antibodies against Ro52, Ro60, La, SmB, SmD, RNP‐70k, RNP‐A, RNP‐C, CENP‐C, Scl‐70, Jo‐1, ribosomal RNP and histones was investigated in 193 mothers of children with AV block by immunoblotting and ELISA. Autoantibody reactivity was detected in 48% (93/193) of the mothers of children with AV block. In autoantibody‐positive mothers, the vast majority, 95% (88/93), had antibodies against Ro52, while 63% (59/93) had autoantibodies to Ro60 and 58% (54/93) had autoantibodies to La. In addition, 13% (12/93) of the autoantibody‐positive mothers had antibodies to other investigated antigens besides Ro52, Ro60 and La, and of these anti‐histone antibodies were most commonly represented, detected in 8% (7/93) of the mothers. In conclusion, this Swedish population‐based study confirms that maternal autoantibodies may associate with heart block in the child. Further, our data demonstrate a dominant role of Ro52 antibodies in association with AV block.

Phrenic and Vagal Nerve Activities during Spontaneous Respiration and Positive‐Pressure Ventilation

Afferent vagal nerve activity from stretch‐receptors in the lung and efferent phrenic nerve activity were recorded during spontaneous respiration and during positive‐pressure ventilation with three different types of ventilators. During spontaneous respiration the efferent phrenic nerve activity slightly preceded the afferent vagal nerve activity. Volume‐controlled ventilation did not alter the phrenic nerve activity when the ventilation was set at a rate equal to that during spontaneous respiration, but afferent vagal volleys increased in duration. At higher frequencies of insufflation spontaneous inspiration was inhibited.

Assisted Mechanical Ventilation Using Elastic Unloading: A Study in Cats with Normal and Injured Lungs

ABSTRACT: Elastic unloading [otherwise known as negative ventilator compliance (Cv) or proportional assist ventilation] is a new mode of assisted mechanical ventilation. The ventilator continuously measures the volume of spontaneous breathing (V) and adjusts the pressure at the airway opening in proportion to V. The quotient of pressure above the baseline end-expiratory level per unit of V (the gain of the assist) is constant at any point in time and can be preset. The apparatus used for this study can also generate clastic loading (positive Cv) by decreasing the pressure at the airway opening in proportion to V. This might be useful during the weaning process. This study compares measured values of total compliance of the combined lung-respirator system (Ctot) with values predicted according to theory, where 1/Ctot = 1/Cv + 1/Cv with C1 being the lung compliance. Respiratory mechanical data were derived from esophagcal pressure and airflow in eight anesthetized, intubatcd, spontaneously breathing cats. Different Cv, levels were set on the ventilator both before and after lung injury with xanthine oxidase. The difference (mean ± SD) between the measured and predicted Ctot was 1.4 ± 21.4% (healthy lungs) and −11.6 ± 14.1% (injured lungs) during unloading and 2.5 ± 7.5% (healthy lungs) during elastic loading. An elevation of Ctot decreased the expiratory airflow. Tidal volume increased slightly in healthy lungs and arterial Pco2 decreased. We conclude that the effects of Cv on the total compliance of the combined lung-respirator system can accurately be predicted.

The Influence of the Ventilatory Pattern on Ventilation, Circulation and Oxygen Transport during Continuous Positive-Pressure Ventilation An Experimental Study

In IPPV, the ventilatory pattern produced by the ventilator and the lung systems is known to influence pulmonary and cardiovascular functions. In this study on dogs the ventilatory pattern of a conventional respirator (Siemens‐Elema Servo Ventilator 900=SV‐900) constituted the norm for comparison with that produced by a system for volume‐controlled HFPPV. The experimental conditions were kept identical (pentobarbital anaesthesia and normoventilation, i.e. arterial PCO2=40 mm Hg, pH=7.4 and constant FIO2 of the inspired air).

High-Frequency Positive-Pressure Ventilation (HFPPV) Applied for Small Lung Ventilation and Compared with Spontaneous Respiration and Continuous Positive Airway Pressure (CPAP)

The respiratory and circulatory conditions in high‐frequency positive‐pressure ventilation (HFPPV) in the dog and during routine surgery in man have been investigated previously. From this previous experimental and clinical experience, the insufflation‐expiratory systems could be modified for small lung ventilation (HFPPV‐infant), and the insufflation frequency‐insufflation time systems could be combined into one function. This modified HFPPV system works without any separate insufflation catheter. The respiratory and circulatory conditions during ventilation with this modified system were investigated in a series of healthy cats anaesthetized with pentobarbital.

Lung Hyaluronan and Water Content in Preterm and Term Rabbit Pups Exposed to Oxygen or Air

Rabbit pups were delivered by cesarean section 1 or 2 d before term, or vaginally around term, and then reared in room air or exposed to intermittent or continuous hyperoxia (>85%) for up to 9 d. Pups were killed at different ages, and lung hyaluronan (HA; µg/g of dry lung weight) and lung water content, measured as wet/dry lung weight, were determined. Compared with the day of birth, the lung HA concentration did not change significantly on succeeding days in pups kept in air delivered 2 d (-2 d) or 1 d (-1 d) before term, whereas the water content decreased significantly. Continuous exposure to hyperoxia resulted in a significantly raised lung HA concentration 6 d postterm in both -2 d and -1 d pups, and intermittent exposure to hyperoxia resulted in a significantly raised HA concentration 6 d postterm in -1 d pups, compared with the groups exposed to room air. These increases were accompanied by significantly elevated wet/dry lung weight ratios. Microscopic examination revealed significantly increased HA staining scores in alveoli, arterioles, and bronchioli in both hyperoxia-exposed groups of -2 d pups 6 d postterm, and nonsignificantly higher scores in -1 d and vaginally delivered pups of comparable age, compared with the scores at birth. The results indicate that oxygen exposure neonatally may result in an increase in lung HA accompanied by an increase in lung water content. The increase in lung HA concentration in our study may be an affect of oxygen free radicals or oxygen-induced stimulation of inflammatory mediators.

Continuous Positive Airway Pressure Increases Vagal and Phrenic Nerve Activity in Cats

To investigate how continuous positive airway pressure (CPAP) changes the vagal nerve activity and whether CPAP alters the efferent phrenic nerve activity or the breathing pattern similarly before and after vagotomy, a study was made of vagal and phrenic nerve activity in chloralose‐anaesthetized cats. In the vagal nerve, CPAP increased the mean impulse frequency during expiratory rest. The breath‐related impulse frequency also increased with CPAP. With higher CPAP (≥ 0.5 kPa), the peak of breath‐induced activity in the vagal nerve lasted longer than inspiration. In the phrenic nerve, the impulse frequency in the bursts increased almost linearly with CPAP irrespective of whether the vagal nerves were intact or not. The duration of the phrenic nerve bursts decreased with increasing CPAP when the vagal nerves were intact. When the vagal nerves were cut, the burst duration did not change. The rate of breathing was almost unchanged by CPAP regardless of whether the vagal nerves were cut or not. The inspiration/expiration ratio decreased with increasing CPAP when the vagal nerves were intact, but not when they were cut.