Lars Eriksson

Comparison of ultrasound and autopsy findings in pregnancies terminated due to fetal anomalies

Objective. To compare antenatal diagnoses with autopsy findings in pregnancies terminated after ultrasound detection of fetal anomalies. A second aim was to study the quality of antenatal fetal diagnosis over time. Design. Retrospective, multicenter study over two consecutive six‐year periods in Uppsala and Stockholm. Setting. Cases were identified through fetal autopsy reports. Subjects. Three hundred and twenty‐eight fetuses from pregnancies terminated between 1992 and 2003 because of ultrasonographically diagnosed anomalies. Main outcome measures. The findings at the last ultrasound examination were compared with the autopsy reports. Results. In 299 cases (91.2%) ultrasound findings either exactly matched or were essentially similar to the autopsy findings. In 23 cases (7%) ultrasound findings were not confirmed at autopsy, but the postnatal findings were at least as severe as the antenatal ones. In six cases (1.8%) termination was performed for an anomaly which proved to be less severe than was predicted by ultrasound. The number of such cases was the same in both six‐year periods, while the total number of cases increased from 113 in the first to 215 in the second period. Fetal examination provided further diagnostic information in 47% of the cases. In 10% a syndrome was disclosed. Conclusion. Termination of pregnancy was not always based on a correct antenatal diagnosis. All fetuses but one from terminated pregnancies had evident anomalies. In six cases (1.8%) the decision to terminate was based on suboptimal prognostic and diagnostic information. Fetal autopsy by an experienced perinatal pathologist is essential to provide a definitive diagnosis.

Selective Loss of Cerebral Keratan Sulfate in Alzheimer's Disease

Proteoglycans, especially heparan sulfate-substituted species, are known to be associated with the deposition of amyloid in Alzheimers disease. We previously found that heparan sulfate from afflicted brains, and from control subjects, differed minimally in quantity and structure (Lindahl, B., Eriksson, L., and Lindahl, U. (1995) Biochem. J. 306, 177-184). In the present study, a glycosaminoglycan fraction, shown to contain heparan sulfate and keratan sulfate, was radiolabeled by partial N-deacetylation (hydrazinolysis) followed by re-N-acetylation using [3H]acetic anhydride. Quantitation of the 3H-labeled polysaccharides, based on digestion with heparitinase I from Flavobacterium heparinum and keratanase from Pseudomonas sp., revealed that the amounts of keratan sulfate in Alzheimer cerebral cortex are reduced to less than half of control values. Moreover, a monoclonal antibody against a highly sulfated keratan sulfate epitope bound to the majority of the neurons in normal cortex but not in the diseased tissue. The lack of highly sulfated keratan sulfate structures may reflect a specific functional defect of the cells.

Sudden unexpected cardiac deaths among young Swedish orienteers - Morphological changes in hearts and other organs.

During the years 1979–1992 an accumulation of sudden unexpected cardiac deaths (SUD) occurred among young Swedish orienteers. A reevaluation of material saved from 16 autopsies was undertaken. Myocarditis was most frequent. It was found in different stages in the majority of cases, indicating subacute or chronic disease with ongoing reparative processes. There were severe morphological changes in all cases. All but one showed a picture of fibrosis and unspecific hypertrophy and/or degenerative changes in myocytes. The hearts were classified into three groups (A‐C), based on the morphological picture of the retrieved heart tissue and the macroscopic description. Group A comprised five cases in which areas with active myocarditis combined with areas of healing or healed myocarditis widely distributed in the left ventricle were the only morphological changes found. Group B comprised four cases demonstrating foci of myocarditis in different stages in the left ventricle and changes resembling those found in arrhythmogenic right ventricular dysplasia (ARVD), including degenerative changes with fibrosis and fatty infiltration located in either ventricle. Group C comprised the remaining seven cases. In none of the cases were coronary artery or valvular anomalies present, nor significant coronary sclerosis or changes outside the heart that could cause SUD.

Second trimester ultrasound screening performed by midwives; sensitivity for detection of fetal anomalies

BACKGROUNDnTo assess the sensitivity for detection of fetal anomalies by a second trimester ultrasound screening program performed in a way representative of a majority of Swedish obstetrical departments. The examinations were performed at the ultrasound division of the Department of Obstetrics and Gynecology at the University Hospital of Uppsala, Sweden.nnnMETHODnA prospective study covering a two-year period. Eight thousand two hundred and twenty-eight unselected, consecutive pregnant women (8345 fetuses) were examined. The ultrasound scans were performed at a gestational age of 15-22 weeks by specially trained midwives. All fetal anomalies suspected at the ultrasound screening were recorded. Follow-up of all scanned fetuses was done through neonatal reports, records from the pediatric department, a national malformation registry and autopsies. All live-born infants were followed one year after birth. Main outcome measures were sensitivity, specificity, and positive predictive value for detection of fetal anomalies and prevalence of fetal anomalies.nnnRESULTSnIn all 145 fetuses/infants with confirmed anomalies were identified (prevalence 1.7%). Thirty-two were detected by second trimester ultrasound screening (sensitivity 22.1%). Twenty false positive cases were identified, of which fifteen were ruled out on the same day the suspicion arose and five were transient findings. The specificity was 99.8% and the positive predictive value 61.5%nnnCONCLUSIONSnWhen performing a second trimester ultrasound screening program, prenatal diagnosis of fetal anomalies will be part of the procedure whether this is a primary aim or not. It is therefore of great importance that the pregnant women receive adequate information and that the voluntariness of participation is stressed. In this study the sensitivity was low. Standardizing the scanning procedure (check-list for fetal anatomy) and improving the education of the operators are feasible ways to increase the sensitivity.

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.

205 HYALURONAN AND WATER CONTENT IN THE LUNG OF PRETERM AND TERM INFANTS WHO DIED LESS THAN 24 HOURS AFTER BIRTH

Fetal connective tissue is known to have a very high concentration of hyaluronan (HA) and of water. In rabbit pups the concentration of HA in the lung has its lowest value one day before term gestation (Am J Physiol 260, 1449, 1991). After birth an increase in lung HA is accompanied by an increase in lung water (Ped Res 1992;32: 635& 1994;35:280).AIM: To determine the concentration of HA and water in the lung of infants who died less than 24 hours after birth.RESULTS: The HA concentration in the lungs of infants born after 23-27 gestational weeks (g.w.)ranged between 1030-2832 μg/g dry lung weight(n=8) and in those born after 2 28 g.w. between 374-1875 μg/g(n=21). The relation between HA concentration and gestational age seemed exponential. Lung water content was high in all infants. HA staining in lung structures was more widely spread in very preterm than in more mature infants. A subepithelial lining of HA could be seen in moderately preterm infants.CONCLUSION: The concentration of hyaluronan in the lungs of newborn infants decreased with increasing gestational age at births. The water content of thp lungs of all infants in this study was high.

Antenatal betamethasone administration decreases the lung hyaluronan concentration in preterm rabbit pups.

Maternal treatment with corticosteroids before preterm delivery is effective in reducing the incidence of respiratory distress syndrome and neonatal mortality. We hypothesized that corticosteroids might lower the lung hyaluronan concentration. Twenty-five rabbit dams (term = 31 d) with timed pregnancies were injected s.c. with 0.75 mg of betamethasone or saline (controls) 1 d before delivery. In addition, two dams delivered at 25 d of gestation were injected with 0.75 mg of betamethasone on two consecutive days before delivery. A total of 238 live pups were delivered by preterm cesarean section at 25, 27, 28, or 29 d of gestation and killed immediately. Their lung hyaluronan concentrations were measured with a radiometric assay, and wet/dry lung weight ratios were determined. Lungs of rabbit pups exposed antenatally to betamethasone and delivered at 25 or 27 d of gestation, but not at 28 or 29 d, displayed significantly (p = 0.001 and p = 0.008, respectively) lower hyaluronan concentrations than control pups, accompanied by less intense subepithelial staining for hyaluronan in alveolar walls. There was no significant difference in wet/dry lung weight ratio between pups exposed to one dose of betamethasone and controls. Antenatal corticosteroid exposure lowers the lung hyaluronan concentration in preterm rabbit pups delivered at 25 or 27 d of gestation, but not in those delivered at 28 or 29 d.

Second trimester routine ultrasound and abnormal findings

Objective To estimate the detection rate of abnormal findings, especially fetal anomalies, at second trimester ultrasound screening performed in a way representative of Swedish antenatal clinics.

Amyloid inclusions in choroid plexus epithelial cells. A simple autopsy method to rapidly obtain information on the age of an unknown dead person

Different methods such as X-ray examination of the skeleton and inspection of the teeth have been described for estimation of the age of an unidentified dead person. These methods are more or less exact but the results will not be available until many days after the autopsy. In the present paper, we present a fairly simple method to obtain information on the age of a deceased using amyloid inclusions in the choroid plexus epithelial cells.

Hyaluronan in the Human Neonatal Lung: Association with Gestational Age and Other Perinatal Factors

The aim of this study was to determine the influence of gestational age at birth, postnatal age, specific complications and methods of treatment on the lung hyaluronan concentration in infants. Lung samples and clinical records from 117 infants who died 0–228 days (32 weeks) after preterm or term birth were studied. The lung hyaluronan concentration at death was most strongly associated with the gestational age at birth, an association best described by an exponential function with a negative power coefficient. After adjustments for gestational age, the lung hyaluronan concentration also correlated significantly with birth weight, weight at death, the wet-to-dry lung weight ratio and specific staining for hyaluronan in the pleura. Intrauterine infection was also associated with a significantly higher lung hyaluronan concentration.