Whole-genome sequencing in prenatally detected congenital malformations: prospective cohort study in clinical setting.

OBJECTIVE: To investigate the diagnostic yield of trio whole-genome sequencing (WGS) in fetuses with various congenital malformations referred to a tertiary center for prenatal diagnosis. METHODS: In this prospective study, 50 pregnancies with different congenital malformations, negative for trisomies and causative copy-number variants, were analyzed further with fetal-parental trio WGS analysis. Parents were eligible for inclusion if they accepted further investigation following the detection of isolated or multiple malformations on prenatal ultrasound. Cases with isolated increased nuchal translucency, gamete donation or multiple pregnancy were excluded. WGS with the Illumina Inc. 30× polymerase-chain-reaction-free short-read sequencing included analysis of single-nucleotide variants, insertions and deletions, structural variants, short tandem repeats and copy-number identification of SMN1 and SMN2 genes. RESULTS: A molecular diagnosis was achieved in 13/50 (26%) cases. Causative sequence variants were identified in 12 genes: FGFR3 (n = 2), ACTA1 (n = 1), CDH2 (n = 1), COL1A2 (n = 1), DHCR7 (n = 1), EYA1 (n = 1), FBXO11 (n = 1), FRAS1 (n = 1), L1CAM (n = 1), OFD1 (n = 1), PDHA1 (n = 1) and SOX9 (n = 1). The phenotypes of the cases were divided into different groups, with the following diagnostic yields: skeletal malformation (4/9 (44%)), multisystem malformation (3/7 (43%)), central nervous system malformation (5/15 (33%)) and thoracic malformation (1/10 (10%)). Additionally, two cases carried variants that were considered potentially clinically relevant, even though they were assessed as variants of uncertain significance, according to the guidelines provided by the American College of Medical Genetics and Genomics. Overall, we identified a causative or potentially clinically relevant variant in 15/50 (30%) cases. CONCLUSIONS: We demonstrate a diagnostic yield of 26% with clinical WGS in prenatally detected congenital malformations. This study emphasizes the benefits that WGS can bring to the diagnosis of fetal structural anomalies. It is important to note that causative chromosomal aberrations were excluded from our cohort before WGS. As chromosomal aberrations are a well-known cause of prenatally detected congenital malformations, future studies using WGS as a primary diagnostic test, including assessment of chromosomal aberrations, may show that the detection rate exceeds the diagnostic yield of this study. WGS can add clinically relevant information, explaining the underlying cause of the fetal anomaly, which will provide information concerning the specific prognosis of the condition, as well as estimate the risk of recurrence. A genetic diagnosis can also provide more reproductive choice for future pregnancies. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Home phototherapy for hyperbilirubinemia in term neonates-an unblinded multicentre randomized controlled trial.

The aim of this study was to assess whether home phototherapy was feasible and safe in a cohort of otherwise healthy term-born neonates who fulfilled the criteria for in-hospital phototherapy. This was a randomized controlled trial in which term newborns with a total serum bilirubin of 18-24 mg/dL (300-400 µmol) were randomized to either home phototherapy or conventional in-hospital phototherapy. The primary outcome measurements were safety and efficacy, length of stay and the number of failed treatments. The secondary outcomes were the number of blood samples and weight gain during treatment. One hundred forty-seven patients were recruited, 69 patients randomized to conventional phototherapy and 78 to home phototherapy. The results showed that no patients needed blood exchange and only 4% of the patients allocated to home phototherapy were admitted to the hospital. The duration of phototherapy, length of stay, amount of blood tests and weight change showed no statically significant differences.Conclusion: Home phototherapy could be a safe alternative to inpatient phototherapy for otherwise healthy newborns with hyperbilirubinemia if daily checkups and 24/7 telephone support can be provided. The parents should be informed to contact the hospital immediately if they fail to perform the treatment at home.Trial registration: Clinicaltrials.gov NCT03536078 What is Known: • Phototherapy in the hospital is a safe and effective treatment without major side effects. • Fibre optic equipment has made the choice of home phototherapy possible. What is New: • This is the first randomized controlled trial comparing home phototherapy with hospital phototherapy. • Results indicate that home phototherapy could be considered as a safe and feasible alternative when performed according to instructions given, to hospital treatment for otherwise healthy term newborns.

Association of STAT6 gene variants with food allergy diagnosed by double-blind placebo-controlled food challenges.

This study describes the role of two STAT6 gene variants in food allergy using data of patients and their parents who underwent double-blind placebo-controlled food challenges (DBPCFCs). After quality control, 369 trios were analysed including 262 children (71.0%) with food allergy. Associations were tested by the Family based association test. The A alleles of both SNPs were associated with food allergy (P = .036 and P = .013 for rs324015 and rs1059513, respectively). Furthermore, these A alleles were associated with peanut allergy, higher sIgE levels to both peanut and cow's milk, more severe symptoms and higher eliciting doses during peanut and cow's milk DBPCFCs (all P < .05). In silico analysis indicates that the identified risk variants increase STAT6 expression which stimulates the differentiation of CD4 +  T cells to the Th2 subset. In conclusion, STAT6 variants may be involved in the pathophysiology of food allergy and their role seems to be independent of the allergenic food.

Prediction of the severity of allergic reactions to foods.

BACKGROUND: There is currently considerable uncertainty regarding what the predictors of the severity of diagnostic or accidental food allergic reactions are, and to what extent the severity of such reactions can be predicted. OBJECTIVE: To identify predictors for the severity of diagnostic and accidental food allergic reactions and to quantify their impact. METHODS: The study population consisted of children with a double-blind, placebo-controlled food challenge (DBPCFC)-confirmed food allergy to milk, egg, peanut, cashew nut, and/or hazelnut. The data were analyzed using multiple linear regression analysis. Missing values were imputed using multiple imputation techniques. Two scoring systems were used to determine the severity of the reactions. RESULTS: A total of 734 children were included. Independent predictors for the severity of the DBPCFC reaction were age (B = 0.04, P = .001), skin prick test ratio (B = 0.30, P < .001), eliciting dose (B = -0.09, P < .001), level of specific immunoglobulin E (B = 0.15, P < .001), reaction time during the DBPCFC (B = -0.01, P = .004), and severity of accidental reaction (B = 0.08, P = .015). The total explained variance of this model was 23.5%, and the eliciting dose only contributed 4.4% to the model. Independent predictors for more severe accidental reactions with an explained variance of 7.3% were age (B = 0.03, P = .014), milk as causative food (B = 0.77, P < .001), cashew as causative food (B = 0.54, P < .001), history of atopic dermatitis (B = -0.47, P = .006), and severity of DBPCFC reaction (B = 0.12, P = .003). CONCLUSIONS: The severity of DBPCFCs and accidental reactions to food remains largely unpredictable. Clinicians should not use the eliciting dose obtained from a graded food challenge for the purposes of making risk-related management decisions.

Novel KIAA0753 mutations extend the phenotype of skeletal ciliopathies.

The skeletal ciliopathies are a heterogeneous group of disorders with a significant clinical and genetic variability and the main clinical features are thoracic hypoplasia and short tubular bones. To date, 25 genes have been identified in association with skeletal ciliopathies. Mutations in the KIAA0753 gene have recently been associated with Joubert syndrome (JBTS) and orofaciodigital (OFD) syndrome. We report biallelic pathogenic variants in KIAA0753 in four patients with short-rib type skeletal dysplasia. The manifestations in our patients are variable and ranging from fetal lethal to viable and moderate skeletal dysplasia with narrow thorax and abnormal metaphyses. We demonstrate that KIAA0753 is expressed in normal fetal human growth plate and show that the affected fetus, with a compound heterozygous frameshift and a nonsense mutation in KIAA0753, has an abnormal proliferative zone and a broad hypertrophic zone. The importance of KIAA0753 for normal skeletal development is further confirmed by our findings that zebrafish embryos homozygous for a nonsense mutation in kiaa0753 display altered cartilage patterning.

Assessment of Minimum Important Difference and Substantial Clinical Benefit with the Vascular Quality of Life Questionnaire-6 when Evaluating Revascularisation Procedures in Peripheral Arterial Disease.

OBJECTIVES: Patient reported outcomes are increasingly used to assess outcomes after peripheral arterial disease (PAD) interventions. VascuQoL-6 (VQ-6) is a PAD specific health-related quality of life (HRQoL) instrument for routine clinical practice and clinical research. This study assessed the minimum important difference for the VQ-6 and determined thresholds for the minimum important difference and substantial clinical benefit following PAD revascularisation. MATERIALS AND METHODS: This was a population-based observational cohort study. VQ-6 data from the Swedvasc Registry (January 2014 to September 2016) was analysed for revascularised PAD patients. The minimum important difference was determined using a combination of a distribution based and an anchor-based method, while receiver operating characteristic curve analysis (ROC) was used to determine optimal thresholds for a substantial clinical benefit following revascularisation. RESULTS: A total of 3194 revascularised PAD patients with complete VQ-6 baseline recordings (intermittent claudication (IC) n = 1622 and critical limb ischaemia (CLI) n = 1572) were studied, of which 2996 had complete VQ-6 recordings 30 days and 1092 a year after the vascular intervention. The minimum important difference 1 year after revascularisation for IC patients ranged from 1.7 to 2.2 scale steps, depending on the method of analysis. Among CLI patients, the minimum important difference after 1 year was 1.9 scale steps. ROC analyses demonstrated that the VQ-6 discriminative properties for a substantial clinical benefit was excellent for IC patients (area under curve (AUC) 0.87, sensitivity 0.81, specificity 0.76) and acceptable in CLI (AUC 0.736, sensitivity 0.63, specificity 0.72). An optimal VQ-6 threshold for a substantial clinical benefit was determined at 3.5 scale steps among IC patients and 4.5 in CLI patients. CONCLUSIONS: The suggested thresholds for minimum important difference and substantial clinical benefit could be used when evaluating VQ-6 outcomes following different interventions in PAD and in the design of clinical trials.

Titanium ions form particles that activate and execute interleukin-1ß release from lipopolysaccharide-primed macrophages.

BACKGROUND AND OBJECTIVE: Peri-implantitis is a destructive inflammatory process characterized by destruction of the implant-supporting bone. Inflammasomes are large intracellular multiprotein complexes that play a central role in innate immunity by activating the release of proinflammatory cytokines. Although inflammasome activation has previously been linked to periodontal inflammation, there is still no information on a potential association with peri-implantitis. The aim of this study was to examine cytotoxic and proinflammatory effects, including inflammasome activation, of metals used in dental implants, in an in vitro model, as well as from clinical tissue samples. MATERIAL AND METHODS: Human macrophages were exposed to different metals [titanium (Ti), cobalt, chromium and molybdenum] in a cell-culture assay. Cytotoxicity was determined using the neutral red uptake assay. Cytokine secretion was quantified using an ELISA, and the expression of genes of various inflammasome components was analysed using quantitative PCR. In addition, the concentrations of interleukin-1ß (IL-1ß) and Ti in mucosal tissue samples taken in the vicinity of dental implants were determined using ELISA and inductively coupled plasma mass spectrometry, respectively. RESULTS: Ti ions in physiological solutions stimulated inflammasome activation in human macrophages and consequently IL-1ß release. This effect was further enhanced by macrophages that have been exposed to lipopolysaccharides. The proinflammatory activation caused by Ti ions disappeared after filtration (0.22 µm), which indicates an effect of particles. Ti ions alone did not stimulate transcription of the inflammasome components. The Ti levels of tissue samples obtained in the vicinity of Ti implants were sufficiently high (≥ 40 µm) to stimulate secretion of IL-1ß from human macrophages in vitro. CONCLUSION: Ti ions form particles that act as secondary stimuli for a proinflammatory reaction.

Identification of new TRIP12 variants and detailed clinical evaluation of individuals with non-syndromic intellectual disability with or without autism.

The ubiquitin pathway is an enzymatic cascade including activating E1, conjugating E2, and ligating E3 enzymes, which governs protein degradation and sorting. It is crucial for many physiological processes. Compromised function of members of the ubiquitin pathway leads to a wide range of human diseases, such as cancer, neurodegenerative diseases, and neurodevelopmental disorders. Mutations in the thyroid hormone receptor interactor 12 (TRIP12) gene (OMIM 604506), which encodes an E3 ligase in the ubiquitin pathway, have been associated with autism spectrum disorder (ASD). In addition to autistic features, TRIP12 mutation carriers showed intellectual disability (ID). More recently, TRIP12 was postulated as a novel candidate gene for intellectual disability in a meta-analysis of published ID cohorts. However, detailed clinical information characterizing the phenotype of these individuals was not provided. In this study, we present seven novel individuals with private TRIP12 mutations including two splice site mutations, one nonsense mutation, three missense mutations, and one translocation case with a breakpoint in intron 1 of the TRIP12 gene and clinically review four previously published cases. The TRIP12 mutation-positive individuals presented with mild to moderate ID (10/11) or learning disability [intelligence quotient (IQ) 76 in one individual], ASD (8/11) and some of them with unspecific craniofacial dysmorphism and other anomalies. In this study, we provide detailed clinical information of 11 TRIP12 mutation-positive individuals and thereby expand the clinical spectrum of the TRIP12 gene in non-syndromic intellectual disability with or without ASD.

Development and validation of the preparedness for Colorectal Cancer Surgery Questionnaire: PCSQ-pre 24.

PURPOSE: The aims of the study were to develop and psychometrically evaluate a patient-reported outcome instrument for the measurement of preoperative preparedness in patients undergoing surgery for colorectal cancer. METHODS: This study was conducted in two stages: a) instrument development (item generation, construction of items and domains), empirical verification and b) instrument evaluation. A questionnaire with 28 items measuring preparedness for surgery was developed covering four domains and was tested for content validity with an expert panel and with patients. Psychometric testing of the questionnaire was conducted on 240 patients undergoing elective surgery for colorectal cancer. RESULTS: The scale content validity index of the preparedness items was 0.97. The final version consisted of 24 items measuring 4 subscales: Searching for and making use of information, Understanding and involvement in the care process, Making sense of the recovery process and Support and access to medical care. Confirmatory factor analysis revealed good model fit with standardized factor loadings ranging from 0.58 to 0.97. A well-fitting second-order factor model provided support for a total preparedness score with second-order factor loadings ranging from 0.75 to 0.93. The ordinal alpha values of the four latent factors ranged from 0.92 to 0.96, indicating good internal consistency. The polyserial correlations with the total score were 0.64 (p < 0.01) for the overall preparedness question and 0.37 (p < 0.01) for overall well-being. CONCLUSION: The Swedish Preparedness for Colorectal Cancer Surgery Questionnaire for use in the preoperative phase demonstrated good psychometric properties based on a sound conceptualization of preparedness.

Using routine Haemophilia Joint Health Score for international comparisons of haemophilia outcome: standardization is needed.

INTRODUCTION: Haemophilia Joint Health Score (HJHS) is the most sensitive validated score for physical examination of joint health in haemophilia. HJHS performed at regular intervals can be used for clinical monitoring as well as for comparative outcomes research. AIM: To determine whether routinely collected HJHS could be used to compare outcome of three different prophylactic regimens in children with severe haemophilia A (primary) and which parameters caused variability in HJHS (secondary). METHODS: International retrospective observational multi-centre study comparing routine HJHS in 127 children with severe haemophilia A born from 1995 to 2009, from London, Stockholm and Utrecht centres. Patient and treatment data were collected from the European Paediatric Network for Haemophilia Management registry and patient files. The independent effects of regimens, physiotherapists, age and inhibitor status on HJHS were explored, using multivariable regression analysis. RESULTS: Prophylaxis varied across participating centres, with differences in initial frequency of infusions (1× per week vs. 3× per week), age at reaching infusions ≥3× per week, and dose kg(-1) week(-1) at HJHS assessment. Evaluation at median age of 11 years showed an illogical association of HJHS with treatment regimen: the least intensive regimen had the lowest HJHS. The HJHS increased with age and history of inhibitor, as expected (internal validity). But the comparison of prophylactic regimens was obscured by systematic differences in assessment between physiotherapists, both within and between centres. CONCLUSION: Inter-physiotherapist discrepancies in routine HJHS hamper comparison of scores between treatment regimens. For multi-centre research, additional inter-observer standardization for HJHS scoring is needed.

Can Cobalt(II) and Chromium(III) Ions Released from Joint Prostheses Influence the Friction Coefficient?

Cobalt chromium molybdenum alloys (CoCrMo) are commonly used as articulating components in joint prostheses. In this tribocorrosive environment, wear debris and metal ionic species are released and interact with proteins, possibly resulting in protein aggregation. This study aimed to investigate whether this could have an effect on the friction coefficient in a typical material couple, namely CoCrMo-on-polyethylene. It was confirmed that both Co(II) and Cr(III) ions, and their combination, at concentrations relevant for the metal release situation, resulted in protein aggregation and its concomitant precipitation, which increased the friction coefficient. Future studies should identify the clinical importance of these findings.

Radiative cooling of C7⁻.

The spontaneous and photo-induced neutralization of C7⁻ produced in a laser ablation source was measured in an electrostatic storage ring. The measurements provide three independent determinations of the radiative cooling of the ions, based on the short time spontaneous decay and on the integrated amplitude and the shape of the photo-induced neutralization signal. The amplitude of the photo-induced signal was measured between 0.5 ms and 35 ms and found to depend on photon wavelength and ion storage time. All three signals can be reproduced with identical thermal IR radiative cooling rates with oscillator strengths equal to theoretical predictions. In addition, the measurements provide the excitation energy distribution.

Structure and content in consultations with patients undergoing surgery for colorectal cancer.

PURPOSE: To explore the structure and content of pre-planned consultations as part of the care and treatment of patients undergoing surgery for colorectal cancer. METHODS: The study was based on 50 transcripts of audio-recorded pre-planned consultations between seven patients and 36 healthcare professionals from the time of diagnosis, pre-operative consultation, discharge consultation and pathology report in a colorectal unit. RESULTS: The spread of consultation time between professions was considerable. Total mean consultation time for patients during the care process (7 consultations/patient) was 111 min (range 83-191). The mean consultation time for surgeons was 18 min (7-40), anaesthesiologists 12 min (5-18) and nurses 14 min (5-49). Patients took up 40% of the word space, healthcare professionals used 59% and significant others 1%. Word space changed in such a way that the patient became more active towards the final consultation. Neither during the diagnosis consultation nor during the pre-operative consultation did the patients meet the operating surgeon. Six major subjects emerged: general health, diagnosis, surgical procedure, pre-operative preparations, recovery and treatment and follow-up. CONCLUSIONS: There is a need for clearer structure in the consultations. Most consultations lacked a clear introduction to the subject of the conversation. The study makes it possible to develop methods and structure for supporting conversations in which the patient is given space to help with the difficult issues present after undergoing surgery for colorectal cancer. The study also contributes to providing knowledge of how to organise surgical consultations in order to optimise person-centeredness, teamwork and clinical efficiency.

Mechanical and tribological behavior of silicon nitride and silicon carbon nitride coatings for total joint replacements.

Total joint replacements currently have relatively high success rates at 10-15 years; however, increasing ageing and an active population places higher demands on the longevity of the implants. A wear resistant configuration with wear particles that resorb in vivo can potentially increase the lifetime of an implant. In this study, silicon nitride (SixNy) and silicon carbon nitride (SixCyNz) coatings were produced for this purpose using reactive high power impulse magnetron sputtering (HiPIMS). The coatings are intended for hard bearing surfaces on implants. Hardness and elastic modulus of the coatings were evaluated by nanoindentation, cohesive, and adhesive properties were assessed by micro-scratching and the tribological performance was investigated in a ball-on-disc setup run in a serum solution. The majority of the SixNy coatings showed a hardness close to that of sintered silicon nitride (~18 GPa), and an elastic modulus close to that of cobalt chromium (~200 GPa). Furthermore, all except one of the SixNy coatings offered a wear resistance similar to that of bulk silicon nitride and significantly higher than that of cobalt chromium. In contrast, the SixCyNz coatings did not show as high level of wear resistance.

Fabrication and evaluation of SixNy coatings for total joint replacements.

Wear particles from the bearing surfaces of joint implants are one of the main limiting factors for total implant longevity. Si(3)N(4) is a potential wear resistant alternative for total joint replacements. In this study, Si(x)N(y)-coatings were deposited on cobalt chromium-discs and Si-wafers by a physical vapour deposition process. The tribological properties, as well as surface appearance, chemical composition, phase composition, structure and hardness of these coatings were analysed. The coatings were found to be amorphous or nanocrystalline, with a hardness and coefficient of friction against Si(3)N(4) similar to that found for bulk Si(3)N(4). The low wear rate of the coatings indicates that they have a potential as bearing surfaces of joint replacements. The adhesion to the substrates remains to be improved.

Vacuum Rabi splitting and strong-coupling dynamics for surface-plasmon polaritons and rhodamine 6G molecules.

We report on strong coupling between surface-plasmon polaritons (SPP) and Rhodamine 6G (R6G) molecules, with double vacuum Rabi splitting energies up to 230 and 110 meV. In addition, we demonstrate the emission of all three energy branches of the strongly coupled SPP-exciton hybrid system, revealing features of system dynamics that are not visible in conventional reflectometry. Finally, in analogy to tunable-Q microcavities, we show that the Rabi splitting can be controlled by adjusting the interaction time between waveguided SPPs and R6G deposited on top of the waveguide. The interaction time can be controlled with sub-fs precision by adjusting the length of the R6G area with standard lithography methods.

Treatment of a patient with a nodal peripheral T-cell lymphoma (angioimmunoblastic T-Cell lymphoma) with a human monoclonal antibody against the CD4 antigen (HuMax-CD4).

A patient with a CD4+ refractory peripheral T-cell lymphoma (PTL), subtype angioimmunoblastic T-cell lymphoma (AILD), was treated with a human monoclonal anti-CD4 antibody (HuMax-CD4) iv once weekly for 10 wk. Early during treatment all palpable enlarged lymph nodes disappeared. A decline of normal CD4+ T-cells in the blood mirrored the treatment effect. Shortly after stopping treatment the patient relapsed with new enlarged lymph nodes. This time no antitumor effect was seen when HuMax-CD4 treatment was reinstituted. No severe side effects were observed during the antibody treatment. This case report is the first describing that HuMax-CD4 has antilymphoma activity in PTL and is an interesting drug to study further in patients with CD4+ PTL.

Anti-HERG activity and the risk of drug-induced arrhythmias and sudden death.

AIMS: Drug-induced QTc-prolongation, resulting from inhibition of HERG potassium channels may lead to serious ventricular arrhythmias and sudden death. We studied the quantitative anti-HERG activity of pro-arrhythmic drugs as a risk factor for this outcome in day-to-day practice. METHODS AND RESULTS: All 284,426 case reports of suspected adverse drug reactions of drugs with known anti-HERG activity received by the International Drug Monitoring Program of the World Health Organization (WHO-UMC) up to the first quarter of 2003, were used to calculate reporting odds ratios (RORs). Cases were defined as reports of cardiac arrest, sudden death, torsade de pointes, ventricular fibrillation, and ventricular tachycardia (n = 5591), and compared with non-cases regarding the anti-HERG activity, defined as the effective therapeutic plasma concentration (ETCPunbound) divided by the HERG IC50 value, of suspected drugs. We identified a significant association of 1.93 (95% CI: 1.89-1.98) between the anti-HERG activity of drugs, measured as log10 (ETCPunbound/IC50), and reporting of serious ventricular arrhythmias and sudden death to the WHO-UMC database. CONCLUSION: Anti-HERG activity is associated with the risk of reports of serious ventricular arrhythmias and sudden death in the WHO-UMC database. These findings are in support of the value of pre-clinical HERG testing to predict pro-arrhythmic effects of medicines.

Rotational isomerism of acetic acid isolated in rare-gas matrices: Effect of medium and isotopic substitution on IR-induced isomerization quantum yield and cis-->trans tunneling rate.

Rotational isomerization of acetic acid (CH3COOH) is studied in Ar, Kr, and Xe matrices. The light-induced trans-->cis reaction is promoted using resonant excitation of a number of modes in the 3500-7000 cm(-1) region, and the quantum yields for this process are measured for various acetic acid isotopologues and matrix materials. For excitation of acetic acid at energies above the predicted isomerization energy barrier (> or =4400 cm(-1)), the measured quantum yields are in average 2%-3%, and this is one order of magnitude smaller than the corresponding values known for formic acid (HCOOH). This difference is interpreted in terms of the presence of the methyl group in acetic acid, which enhances energy relaxation channels competing with the rotational isomerization. This picture is supported by the observed large effect of deuteration of the methyl group on the photoisomerization quantum yield. The trans-->cis reaction quantum yields are found to be similar for Ar, Kr, and Xe matrices, suggesting similar energy relaxation processes for this molecule in the various matrices. The IR-induced cis-->trans process, studied for acetic acid deuterated in the hydroxyl group, shows reliably larger quantum yields as compared with the trans-->cis process. For pumping of acetic acid at energies below the predicted isomerization barrier, the trans-->cis reaction quantum yields decrease strongly when the photon energy decreases, and tunneling is the most probable mechanism for this process. For the cis-->trans dark reaction, the observed temperature and medium effects indicate the participation of the lattice phonons in the tunneling-induced process.

Association between low Apgar score and neonatal cholestasis.

AIM: To investigate the association between low Apgar score and the development of cholestasis. METHODS: Seventy-seven cholestatic infants, all referred to our tertiary centre and born between 1987 and 1996 were studied. Twenty-eight patients had biliary atresia (BA), 36 had various intrahepatic disorders and for 13 patients the aetiology of the cholestasis was unknown. Data on gestational age, mode of delivery, Apgar score and birthweight for the cholestatic infants and 1,118,270 control subjects born during the same time period were obtained from the Swedish Medical Birth Registry. If the Apgar score of the cholestatic patient was <7 at 1 min and/or <9 at 5 min and/or <9 at 10 min of age the available medical records were reviewed for signs of neonatal distress. RESULTS: Five cholestatic patients, all of them premature, fulfilled the Apgar criteria. For two of them the low Apgar score and need for immediate resuscitation were explained by major surgical problems. The other three patients, two with biliary atresia (BA) and one with Alagille syndrome, had clinical signs of neonatal distress. The incidence of low Apgar score in BA patients was 7% and in cholestatic patients without known aetiology 0%, neither figure differing significantly from that of the of the control group (2.6%). CONCLUSION: Low Apgar score is not more common in any of the cholestatic groups than in the general Swedish population of newborns. We suggest that aetiological associations other than low Apgar score need to be considered in infants with cholestasis of unknown cause.