Vasoactive intestinal polypeptide regulates barrier function via mast cells in human intestinal follicle-associated epithelium and during stress in rats.

BACKGROUND: Vasoactive intestinal polypeptide (VIP) has been implicated as a regulator of intestinal barrier function and inflammation. Our aim was to elucidate the role of VIP in follicle-associated epithelium (FAE) and villus epithelium (VE) permeability following stress in rats and on human intestinal barrier function. METHODS: Rats were injected intraperitoneally (i.p.) with VIP receptor-antagonists (anti-VPACs), a mast cell stabilizer, doxantrazole (DOX), or NaCl, and submitted to acute water avoidance stress. Ileal segments were mounted in Ussing chambers to assess (51) chromium-edta ((51) Cr-edta) and Escherichia (E.) coli (strain K-12) permeability. Rat ileal and human ileal and colonic segments were exposed to VIP ± anti-VPACs or DOX. An in vitro co-culture model of human FAE was used to study epithelial-VIP effects. VIP/VPACs distribution was assessed by microscopy. KEY RESULTS: Stress increased (51) Cr-edta and E. coli permeability in VE and FAE. The increases were abolished by i.p. injection of DOX or anti-VPACs. Ileal VIP-exposure ex vivo increased bacterial passage and this was reduced by DOX. In human FAE ex vivo, VIP treatment doubled bacterial uptake, which was normalized by DOX or anti-VPACs. No barrier effects were observed in human colonic tissue. VPACs were found in rat and human ileal follicles, with partial mast cell co-localization. The co-culture model confirmed VIP-mast cell-epithelial interactions in the regulation of barrier function. CONCLUSIONS & INFERENCES: Stress affects the FAE barrier by mechanisms involving VIP and VPACs on mucosal mast cells. We suggest a regulatory role for VIP in the control of ileal permeability that may be relevant to bacterial-epithelial interactions in stress-related intestinal disorders.

Computed tomography analysis of radiostereometric data to determine flexion axes after total joint replacement: application to the elbow joint.

Kinematic analysis for in vivo assessment of elbow endoprostheses requires knowledge of the exact positions of motion axes relative to bony landmarks or the prosthesis. A prosthesis-based reference system is required for comparison between individuals and studies. The primary aim of this study was to further develop an earlier described algorithm for fusion of radiostereometric analysis (RSA) data and data obtained in 3D computed tomography (CT) for application to the elbow after total joint replacement. The secondary aim was to propose a method for marking of prostheses in 3D CT, enabling definition of a prosthesis-based reference system. Six patients with elbow endoprostheses were investigated. The fusion of data made it possible to visualize the motion axes in relation to the prostheses in the 3D CT volume. The differences between two repeated positioning repetitions of the longitudinal prosthesis axis were less than 0.6 degrees in the frontal and sagittal planes. Corresponding values for the transverse axis were less than 0.6 degrees in the frontal and less than 1.4 degrees (in four out of six less than 0.6 degrees ) in the horizontal plane. This study shows that by fusion of CT and RSA data it is possible to determine the accurate position of the flexion axes of the elbow joint after total joint replacement in vivo. The proposed method for implant marking and registration of reference axes enables comparison of prosthesis function between patients and studies.

Stress-induced barrier disruption of rat follicle-associated epithelium involves corticotropin-releasing hormone, acetylcholine, substance P, and mast cells.

BACKGROUND: The follicle-associated epithelium (FAE) is specialized in uptake and sampling of luminal antigens and bacteria. We previously showed that stress increased FAE permeability in rats. An increased uptake may alter antigen exposure in Peyer's patches leading to intestinal disease. The aim of this study was to elucidate mechanisms involved in the acute stress-induced increase in FAE permeability. METHODS: Rats were pretreated i.p. with corticotropin-releasing hormone receptor (CRH-R) antagonist, neurokinin receptor 1 (NK-1R) antagonist, atropine, the mast cell stabilizer doxantrazole (DOX), or NaCl, and submitted to 1-h acute water avoidance stress. FAE tissues were mounted in Ussing chambers for measurements of permeability to (51)Cr-EDTA, horseradish peroxidase (HRP) and chemically killed Escherichia coli K-12. Further, FAE segments were exposed in vitro in chambers to CRH, substance P (SP), carbachol, and DOX. Neurotransmitter- and receptor distribution was studied by immunohistochemistry. KEY RESULTS: Stress-induced increases in uptake across FAE of HRP and E. coli were reduced by DOX, CRH-R antagonist and atropine, whereas the NK-1R antagonist decreased (51)Cr-EDTA permeability. Exposure to CRH and carbachol increased HRP and E. coli passage, whereas SP increased bacterial and (51)Cr-EDTA permeability. DOX counteracted all of these effects. Immunohistochemistry revealed CRH, acetylcholine, SP, and their receptors on mast cells within the Peyer's patches, subepithelial dome, and adjacent villi. CONCLUSIONS & INFERENCES: Corticotropin-releasing hormone and acetylcholine signaling affect mainly transcellular permeability while SP seems more selective toward the paracellular pathways. Our findings may be of importance for the understanding of the pathogenesis of stress-related intestinal disorders.

The effects of capsaicin on gastrin secretion in isolated human antral glands: before and after ingestion of red chilli.

BACKGROUND: Capsaicin is known to have regulatory effects on gastrointestinal functions via the vanilloid receptor (VR1). We reported previously that endocrine-like cells in the human antrum express VR1. AIM: To identify VR1-expressing endocrine-like cells in human antral glands and to examine whether stimulation with capsaicin causes release of gastrin, somatostatin, and serotonin. Further, to investigate the effects of a chilli-rich diet. METHODS: Gastroscopic biopsies were received from 11 volunteers. Seven of the 11 subjects agreed to donor gastric biopsies a second time after a 3-week chilli-rich diet containing 1.4-4.2 mg capsaicin/day. VR1-immunoreactive cells were identified by double-staining immunohistochemistry against gastrin, somatostatin, and serotonin. For the stimulation studies, we used an in vitro method where antral glands in suspension were stimulated with 0.01 mM capsaicin and physiological buffer was added to the control vials. The concentrations of secreted hormones were detected and calculated with radioimmunoassay (RIA). Results The light microscopic examination revealed that VR1 was localized in gastrin cells. The secretory studies showed an increase in release of gastrin and somatostatin compared to the control vials (P = 0.003; P = 0.013). Capsaicin-stimulation caused a consistent raise of the gastrin concentrations in the gland preparations from all subjects. A chilli-rich diet had an inhibitory effect on gastrin release upon stimulation compared to the results that were obtained before the start of the diet. CONCLUSION: This study shows that capsaicin stimulates gastrin secretion from isolated human antral glands, and that a chilli-rich diet decreases this secretion.

Corticotropin-releasing hormone (CRH) regulates macromolecular permeability via mast cells in normal human colonic biopsies in vitro.

OBJECTIVE: Persistent stress and life events affect the course of ulcerative colitis and irritable bowel syndrome by largely unknown mechanisms. Corticotropin-releasing hormone (CRH) has been implicated as an important mediator of stress-induced abnormalities in intestinal mucosal function in animal models, but to date no studies in human colon have been reported. The aim was to examine the effects of CRH on mucosal barrier function in the human colon and to elucidate the mechanisms involved in CRH-induced hyper-permeability. DESIGN: Biopsies from 39 volunteers were assessed for macromolecular permeability (horseradish peroxidase (HRP), (51)Cr-EDTA), and electrophysiology after CRH challenge in Ussing chambers. The biopsies were examined by electron and confocal microscopy for HRP and CRH receptor localisation, respectively. Moreover, CRH receptor mRNA and protein expression were examined in the human mast cell line, HMC-1. RESULTS: Mucosal permeability to HRP was increased by CRH (2.8+/-0.5 pmol/cm(2)/h) compared to vehicle exposure (1.5+/-0.4 pmol/cm(2)/h), p = 0.032, whereas permeability to (51)Cr-EDTA and transmucosal electrical resistance were unchanged. The increased permeability to HRP was abolished by alpha-helical CRH (9-41) (1.3+/-0.6 pmol/cm(2)/h) and the mast cell stabilizer, lodoxamide (1.6+/-0.6 pmol/cm(2)/h). Electron microscopy showed transcellular passage of HRP through colonocytes. CRH receptor subtypes R1 and R2 were detected in the HMC-1 cell line and in lamina propria mast cells in human colon. CONCLUSIONS: Our results suggest that CRH mediates transcellular uptake of HRP in human colonic mucosa via CRH receptor subtypes R1 and R2 on subepithelial mast cells. CRH-induced macromolecular uptake in human colon mucosa may have implications for stress-related intestinal disorders.

Fusion of radiostereometric analysis data into computed tomography space: application to the elbow joint.

Improvement of joint prostheses is dependent upon information concerning the biomechanical properties of the joint. Radiostereometric analysis (RSA) and electromagnetic techniques have been applied in previous cadaver and in vivo studies on the elbow joint to provide valuable information concerning joint motion axes. However, such information is limited to mathematically calculated positions of the axes according to an orthogonal coordinate system and is difficult to relate to individual skeletal anatomy. The aim of this study was to evaluate the in vivo application of a new fusion method to provide three-dimensional (3D) visualization of flexion axes according to bony landmarks. In vivo RSA data of the elbow joint's flexion axes was combined with data obtained by 3D computed tomography (CT). Results were obtained from five healthy subjects after one was excluded due to an instable RSA marker. The median error between imported and transformed RSA marker coordinates and those obtained in the CT volume was 0.22 mm. Median maximal rotation error after transformation of the rigid RSA body to the CT volume was 0.003 degrees . Points of interception with a plane calculated in the RSA orthogonal coordinate system were imported into the CT volume, facilitating the 3D visualization of the flexion axes. This study demonstrates a successful fusion of RSA and CT data, without significant loss of RSA accuracy. The method could be used for relating individual motion axes to a 3D representation of relevant joint anatomy, thus providing important information for clinical applications such as the development of joint prostheses.

Increased antigen and bacterial uptake in follicle associated epithelium induced by chronic psychological stress in rats.

BACKGROUND: Chronic stress affects the course of inflammatory bowel disease and experimental colitis, and may also initiate intestinal inflammation in rats. AIM: To investigate the effects of stress on the M cell containing follicle associated epithelium, specialised in antigen uptake. SUBJECTS AND METHODS: Wistar rats were submitted to acute water avoidance stress for one hour or chronic water avoidance stress for 1 hour/day for 10 consecutive days. Permeability to (51)Cr-EDTA, horseradish peroxidase, and chemically killed Escherichia coli K-12 was studied in both villus and follicle associated epithelium in Ussing chambers. Segments were further examined by light, electron, and confocal microscopy. RESULTS: Acute stress increased horseradish peroxidase flux in villus as well as in follicle associated epithelium. Chronic stress further increased permeability to horseradish peroxidase in villus and follicle associated epithelium, in the latter by almost fourfold. Moreover, chronic stress induced over 30 times increased E coli passage in follicle associated epithelium whereas there was no significant increase in villus epithelium. Bacterial uptake was confirmed by confocal microscopy showing fluorescent bacteria penetrating and passing through the epithelial surface. CONCLUSIONS: These results show that the barrier function of follicle associated epithelium can be modulated, and that chronic stress enhances the uptake of luminal antigens and bacteria via the follicle associated epithelium. This can increase antigen exposure in Peyer's patches thereby having implications in the initiation of proinflammatory immune responses within the intestinal mucosa.

Variation in the position and orientation of the elbow flexion axis.

We analysed the axis of movement in the normal elbow during flexion in vivo using radiostereometric analysis (RSA). The results show an intraindividual variation in the inclination of the axis ranging from 2.1 degrees to 14.3 degrees in the frontal and from 1.6 degrees to 9.8 degrees in the horizontal plane analysed at 30 degrees increments. The inclination of the mean axis of rotation varied within a range of 12.7 degrees in the frontal and 4.6 degrees in the horizontal plane. In both planes, the mean axes were located close to a line joining the centres of the trochlea and capitellum. The intra- and interindividual variations of the axes of flexion of the elbow were greater than previously reported. These factors should be considered in the development of elbow prostheses.

Synaptology of trigemino- and spinothalamic lamina I terminations in the posterior ventral medial nucleus of the macaque.

We used the electron microscope to examine lamina I trigemino- and spinothalamic (TSTT) terminations in the posterior part of the ventral medial nucleus (VMpo) of the macaque thalamus. Lamina I terminations were identified by anterograde labeling with biotinylated dextran, and 109 boutons on 38 terminal fibers were closely studied in series of ultrathin sections. Five unlabeled terminal boutons of similar appearance were also examined in detail. Three-dimensional, volume-rendered computer models were reconstructed from complete series of serial sections for 29 boutons on 10 labeled terminal fibers and one unlabeled terminal fiber. In addition, postembedding immunogold staining for GABA was obtained in alternate sections through 23 boutons. Lamina I TSTT terminations in VMpo generally have several large boutons (mean length = 2.16 microm, mean width = 1.29 microm) that are densely packed with vesicles and make asymmetric synaptic contacts on low-order dendrites of VMpo neurons (mean diameter 1.45 microm). They are closely associated with GABAergic presynaptic dendrites (PSDs), and nearly all form classic triadic arrangements (28 of 29 reconstructed boutons). Consecutive boutons on individual terminal fibers make multiple contacts with a single postsynaptic dendrite and can show evidence of progressive complexity. Dendritic appendages that enwrap and invaginate the terminal bouton constitute additional anatomic evidence for secure, high-fidelity synaptic transfer. These observations provide direct ultrastructural evidence supporting the hypothesis that VMpo is a lamina I TSTT thalamocortical relay nucleus in primates that subserves pain, temperature, itch, and other sensations related to the physiological condition of the body.

Hospital care utilization of infants born after IVF.

BACKGROUND: Infants born after IVF are often twins, and singleton IVF babies have an increased risk for preterm birth. Both conditions are likely to increase morbidity. We examined the frequency and duration of hospitalization required by babies born after IVF, and compared this information with all infants born in Sweden during the same time period. METHODS: We used a nationwide registration of IVF pregnancies from 1984 to 1997 and a nationwide register of all in-patient care up to the end of 1998. We identified 9056 live born infants after IVF treatment and compared them with 1 417 166 non-IVF live born infants. RESULTS: The highest odds ratio (OR approximately 3) was seen for neonatal hospitalization, but an increased OR (1.2-1.3) was noted for children up to 6 years of age. The OR for being hospitalized after IVF was 1.8, but when the analysis was restricted to term infants it was 1.3 and this excess was then explainable by maternal subfertility. Statistically significant increased ORs were seen for hospitalization for cerebral palsy (1.7), epilepsy (1.5), congenital malformation (1.8) or tumour (1.6), but also for asthma (1.4) or any infection (1.4). When information from the Swedish Cancer Registry was used, no excess risk for childhood cancer was found. The average number of days spent in hospital by IVF and non-IVF children was 9.5 and 3.6 respectively. CONCLUSIONS: The increased hospitalization of IVF children is, to a large extent, due to the increased incidence of multiple births. Therefore, the increased costs associated with this may be reduced by the use of single embryo transfers, with the savings in health care costs being offset against the increased number of embryo transfer cycles required to maintain the pregnancy rate.

Neurological sequelae in children born after in-vitro fertilisation: a population-based study.

BACKGROUND: There is an absence of population-based long-term studies on the risk of neurological sequelae in children born after in-vitro fertilisation (IVF). Our aim was to compare the frequency of such problems between IVF-born children and controls. METHODS: We did a population-based retrospective cohort study in which we compared development of neurological problems in 5680 children born after IVF, with 11360 matched controls. For 2060 twins born after IVF, a second set of controls (n=4120), all twins, were selected. We obtained data on neurological problems from the records of the Swedish habilitation centres. FINDINGS: Children born after IVF are more likely to need habilitation services than controls (odds ratio 1.7, 95% CI 1.3-2.2). For singletons, the risk was 1.4 (1.0-2.1). The most common neurological diagnosis was cerebral palsy, for which children born after IVF had an increased risk of 3.7(2.0-6.6), and IVF singletons of 2.8 (1.3-5.8). Suspected developmental delay was increased four-fold (1.9-8.3) in children born after IVF. Twins born after IVF did not differ from control twins with respect to risk of neurological sequelae. Low-birthweight and premature infants were more likely to need habilitation than fullterm babies. Maternal age did not affect risk. INTERPRETATION: Our study suggests that children born after IVF have an increased risk of developing neurological problems, especially cerebral palsy. These risks are largely due to the high frequency of twin pregnancies, low birthweight, and prematurity among babies born after IVF. To limit these risks, we recommend that only one embryo should be transferred during IVF.

Morphological support for paracrine inhibition of gastric acid secretion by nitric oxide in humans.

BACKGROUND: Functional studies have shown that nitric oxide (NO) inhibits gastric acid secretion in a variety of species, including man. We have performed a morphological study with the intention of localizing the endothelial NO synthase (eNOS) in the human gastric mucosa. METHODS: Fifteen healthy subjects voluntarily participated in the study, and mucosal biopsies were obtained from the cardia, corpus and antrum. The presence and localization of eNOS were studied using immunohistochemical techniques. RESULTS: eNOS-immunoreactivity (eNOS-IR) is found in surface mucous cells of cardia, corpus and antrum. Unique to the oxyntic mucosa is the presence of eNOS-IR in 'endocrine-like' cells, found in close contact with parietal cells. CONCLUSIONS: eNOS-IR cells in close apposition to parietal cells provide morphological support for paracrine inhibition of gastric acid secretion by NO.

Use of multivitamins and folic acid in early pregnancy and multiple births in Sweden.

Folic acid is recommended to reduce the risk of neural tube defects and other congenital malformations. Data from the Swedish Medical Birth Registry were used to study frequency of twinning in women who in early pregnancy reported the use of folic acid. Women (n = 2,569) who in early pregnancy reported the use of folic acid had an increased rate of twin deliveries after consideration of maternal age and of length of involuntary childlessness, both variables being significant confounders. The effect of folic acid was seen also in women who did not report involuntary childlessness. A similar but not statistically significant trend was seen after use of multivitamins without simultaneous use of folic acid tablets (n = 1,979). The increased risk seems to be limited to dizygotic twinning (relative risk = 2.13, 95% CI 1.64-2.74). If this association is causal, wide-spread supplementation with folic acid may represent a hazard larger than the postulated beneficial effect on neural tube defects, at least in low-risk areas.

Nonsteroidal anti-inflammatory drugs in early pregnancy.

A study was performed of congenital malformations in infants whose mothers used nonsteroidal anti-inflammatory drugs (NSAIDs) in early pregnancy. Data were obtained from an ongoing prospective recording of drug use during the first trimester. During the period July 1, 1995 through December 31, 1998, 2557 infants were born to women who reported the use of NSAIDs in early pregnancy. The OR (after consideration of maternal age, parity, and smoking habits) for any congenital malformation was 1.04 (95%CI 0.84-1.29), but the OR for cardiac defects reported to the Medical Birth Registry was 1.86 (1.32-2.62) based on 36 instances, and for orofacial clefts 2.61 (1.01-6.78) based on only six instances. By using other information sources, another four infants with cardiac defects were identified. There was no drug specificity for cardiac defects but among six mothers of infants with orofacial clefts, five had used naproxen.

Congenital malformations in infants born after IVF: a population-based study.

The presence of congenital malformations in infants born after IVF was studied from a register consisting of practically all infants born in Sweden after IVF, 1982--1997 (n = 9111). A further 64 infants were studied using only medical records. It is a nation-wide study and has a population-based control group (n = 1,690,577) and relevant potential confounders have been taken into account. There was an excess of congenital malformations registered in the Medical Birth Registry (n = 516, odds ratio = 1.47) but this excess disappeared when confounders were taken into consideration: year of birth, maternal age, parity, and period of unwanted childlessness (odds ratio = 0.89). For some specific conditions, an approximately 3-fold excess risk was seen: neural tube defects, alimentary atresia, omphalocele, and hypospadias (after intracytoplasmatic sperm injection). No excess risk for hypospadias was seen after standard IVF. Various explanations for these findings are discussed. It is postulated that the excess risk for alimentary atresia, like the excess risk for monozygotic twinning after IVF, is a direct consequence of the IVF procedure. The excess risk for hypospadias after ICSI may be related to paternal subfertility with a genetic background. The absolute risk for a congenital malformation in association with IVF is small.

Deliveries and children born after in-vitro fertilisation in Sweden 1982-95: a retrospective cohort study.

BACKGROUND: In-vitro fertilisation is an effective treatment for infertility, but there is concern about the health of children. We investigated, in a retrospective registry study, malformations, cancers, and deaths in the complete Swedish in-vitro-fertilisation birth cohort compared with the general population. METHODS: We collected data from all in-vitro-fertilisation clinics in Sweden and compared the obstetric outcomes of babies (n=5856) born between 1982 and 1995 with all babies born in the general population (n=1,505,724) during the same period, according to data from the Swedish Medical Birth Registry and the Registry of Congenital Malformations. We investigated the incidence of childhood cancer through the Swedish Cancer Registry. Data were stratified for maternal age, parity, previous subfertility, year of birth, and multiple of pregnancies. FINDINGS: Multiple births occurred in 27% of pregnancies compared with 1% in the control group. In the in-vitro-fertilisation group, more babies were born preterm (<37 weeks) than controls (30.3 vs 6.3%) and more had low birthweights (<2500 g, 27.4 vs 4.6%). The perinatal mortality was 1.9% in the in-vitro fertilisation group and 1.1% in the controls. For in-vitro-fertilisation singletons, the risk ratios, adjusted for year of birth, for very preterm birth (<32 weeks) and very low birthweight (<1500 g) were 3.54 (95% CI 2.90-4.32) and 4.39 (3.62-5.32), respectively. Malformations occurred in 5.4% of all babies in the in-vitro-fertilisation group (1.39 [1.25-1.54]), and the rates of neural-tube defects and oesophageal atresia were higher than those in the controls. There was no increase in childhood cancer in the in-vitro-fertilisation group. INTERPRETATION: A high frequency of multiple births and maternal characteristics were the main factors that led to adverse outcomes, and not the in-vitro-fertilisation technique itself. The clinical practice of in-vitro-fertilisation needs to be changed to lower the rate of multiple pregnancy.

[Health care registries a community asset. Centralized registries of health care data can save life and improve quality of life]. / Dataregister i vården en kollektiv nyttighet. Centrala hälsodataregister kan rädda liv och förbättra livskvalitet.

The article is a review of how national epidemiological data bases in Sweden can be used for research and statistical purposes. Over 500 major applications from research groups and others are dealt with annually by the National Cancer, Hospital discharge, Medical birth, and Cause-of-death registries, providing essential data for studies which have yielded well over a thousand peer-reviewed scientific papers. In over 40 years' Swedish experience of administering the registration of sensitive patient-specific information on diseases, there has not been a single case of data misuse. It is concluded that the benefits of national epidemiological registries far outweigh the risks and marginal costs of maintaining them.

Delivery outcome after the use of antidepressants in early pregnancy.

OBJECTIVES: To investigate delivery outcome after the use of antidepressants in early pregnancy. METHODS: Using an ongoing prospective recording of drug use in early pregnancy, 969 women were identified who reported the use of antidepressants: 531 used only SSRI (selective serotonin re-uptake inhibitor) drugs (mostly citalopram, 375 exposures), 423 used only other antidepressants, and 15 used both. Outcome was compared with all births in the population. RESULTS: Women using these drugs were older and smoked more than three times as often as other women. There seemed to be an excess of high parity women. The frequency of multiple births was lower than expected, resulting from too few twin births in women who had used SSRI. Gestational duration among singletons was shorter but it did not affect infant survival and was similar after the use of SSRI or non-SSRI antidepressants, perhaps the result of uncompensated for confounding or related to the underlying disease. Infants were somewhat heavier than expected, notably after non-SSRI treatment. No increase was seen in congenital abnormalities, observable in the perinatal period. CONCLUSIONS: Based on this database, the use of antidepressants in early pregnancy does not seem to carry any significant risk for the infant that is detectable during the newborn period.

Blood transfusion at delivery and risk of subsequent malignant lymphoma in the mother.

BACKGROUND AND OBJECTIVES: Blood transfusion has been shown to be a risk factor for non-Hodgkin's lymphoma (NHL). MATERIALS AND METHODS: In a cohort of 77,928 women with bleeding complications at delivery in the period of 1973-1986, subsequent NHL cases were identified and the number was compared with the number expected from national incidence rates. In a case-control study the proportion of transfused NHL cases was compared with the proportion of transfused controls. RESULTS: The observed number of NHL in the cohort was 18 versus 22.0 expected. Information on transfusion was obtained for 15 of the NHL cases and none (0%) was transfused versus 32 out of 136 controls (23%). CONCLUSIONS: Blood transfusion at delivery is not a risk factor for NHL. The immune tolerance induced by pregnancy may reduce the risk of NHL associated with the transfusion of allogeneic blood cells.

Very low birthweight boys at the age of 19.

Using linked data from the Swedish Medical Birth Registry and the National Service Enrollment Register, long term follow up (to 18-19 years age) was made of 260 surviving singleton boys whose birthweight was less than 1500 g from a total of 150 229 boys born between 1973-5. These boys were shorter and lighter than boys who weighed more at birth, they had more visual and hearing impairments, were at much higher risk of cerebral palsy and other signs of mental impairment, evident as lower intelligence test scores and shorter schooling. No significant excess of asthma, back problems, or headaches were found.