Adverse outcome following selective termination of presenting twin vs non-presenting twin.

OBJECTIVE: Data are lacking on the impact on pregnancy outcome of the position of the abnormal fetus in a discordant twin pregnancy undergoing selective termination (ST). Tissue maceration post ST of the presenting twin may lead to early rupture of membranes, amnionitis and preterm labor. The aim of this study was to evaluate pregnancy complications and outcome following ST of the presenting vs non-presenting twin. METHODS: This was a multicenter retrospective cohort study of dichorionic diamniotic twin pregnancies that underwent ST due to a discordant fetal anomaly (structural or genetic) between 2007 and 2021. The study population was divided into two groups according to the position of the reduced twin (presenting or non-presenting) and outcomes were studied accordingly. The primary outcome was a composite of early complications following ST, including infection, preterm prelabor rupture of membranes and pregnancy loss. RESULTS: A total of 190 dichorionic twin pregnancies were included, of which 73 underwent ST of the presenting twin and 117 of the non-presenting twin. The groups did not differ in either baseline demographic characteristics or mean gestational age at the time of the procedure. ST of the presenting twin resulted in a significantly higher rate of early complications compared with the non-presenting twin (19.2% vs 7.7%; P = 0.018). Moreover, the rates of preterm delivery (75.3% vs 37.6%; P < 0.001) and neonatal intensive care unit admission (45.3% vs 17.1%; P < 0.001) were higher, and birth weight was lower (P < 0.001), in those pregnancies in which the presenting twin was reduced. CONCLUSIONS: ST of the presenting twin resulted in a higher rate of adverse pregnancy outcome compared with that of the non-presenting twin. These findings should be acknowledged during patient counseling and, if legislation permits, taken into consideration when planning ST. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Universal chromosomal microarray analysis reveals high proportion of copy-number variants in low-risk pregnancies.

OBJECTIVES: To evaluate the yield and utility of the routine use of chromosomal microarray analysis (CMA) for prenatal genetic diagnosis in a large cohort of pregnancies with normal ultrasound (US) at the time of genetic testing, compared with pregnancies with abnormal US findings. METHODS: We reviewed all prenatal CMA results in our center between November 2013 and December 2018. The prevalence of different CMA results in pregnancies with normal US at the time of genetic testing ('low-risk pregnancies'), was compared with that in pregnancies with abnormal US findings ('high-risk pregnancies'). Medical records were searched in order to evaluate subsequent US follow-up and the outcome of pregnancies with a clinically relevant copy-number variant (CNV), i.e. a pathogenic or likely pathogenic CNV or a susceptibility locus for disease with > 10% penetrance, related to early-onset disease in the low-risk group. RESULTS: In a cohort of 6431 low-risk pregnancies that underwent CMA, the prevalence of a clinically significant CNV related to early-onset disease was 1.1% (72/6431), which was significantly lower than the prevalence in high-risk pregnancies (4.9% (65/1326)). Of the low-risk pregnancies, 0.4% (27/6431) had a pathogenic or likely pathogenic CNV, and another 0.7% (45/6431) had a susceptibility locus with more than 10% penetrance. Follow-up of the low-risk pregnancies with a clinically significant early-onset CNV revealed that 31.9% (23/72) were terminated, while outcome data were missing in 26.4% (19/72). In 16.7% (12/72) of low-risk pregnancies, an US abnormality was discovered later on in gestation, after genetic testing had been performed. CONCLUSION: Although the background risk of identifying a clinically significant early-onset abnormal CMA result in pregnancies with a low a-priori risk is lower than that observed in high-risk pregnancies, the risk is substantial and should be conveyed to all pregnant women. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Placental hyperinflation and the risk of adverse perinatal outcome.

OBJECTIVES: To determine the pathological basis and clinical associations of excessively thick placentae observed at second-trimester ultrasound examination. METHODS: In a retrospective cohort of 19 singleton high-risk second-trimester pregnancies noted to have a placental length-to-maximum thickness ratio ≤ 2.0, maximum sonographic placental thickness was correlated with clinical outcome, maximum placental thickness after delivery and placental pathological findings. Results were compared with those of an intermediate group of 21 high-risk pregnancies with normal placental dimensions and a control group of 18 low-risk pregnancies also with normal placental dimensions. Increased maximum placental thickness (> 28 mm) and abnormal placental deflation following delivery (pathology - sonography difference in maximum placental thickness < -2 mm) were defined by the upper and lower quartile values, respectively, in the control group. RESULTS: The study group exhibited significantly more adverse outcomes and gross pathological placental features compared with both intermediate and control groups. Despite increased sonographic maximum placental thickness in the study group (median, 55 (range, 40-75) mm compared with both the intermediate group (median, 27 (range, 22-41) mm, P < 0.0001) and the control group (median 26 (range, 23-36) mm, P < 0.0001)), all three groups had similar maximal placental thickness following delivery (study group: median, 24 (range, 10-50) mm vs intermediate group: median, 27 (range, 15-40) mm, P = 0.82 and vs control group: median, 28.5 (range, 18-44), P = 0.42). Pathology-sonography difference in maximum placental thickness in the study group (median, -30 (range, -42 to 0) mm) was significantly greater than that in either the intermediate (median, -2 (range, -11 to 9) mm, P < 0.0001) or the control (median, 1.5 (range, -10 to 18) mm, P < 0.0001) group and was significantly associated with abnormal development of the gas-exchanging placental villi (distal villous hypoplasia) (P = 0.0001). CONCLUSIONS: Increased second-trimester sonographic maximum placental thickness represents a pathological finding associated with severe adverse perinatal outcome. This observation is due to overinflation of the intervillous space by maternal blood rather than to adaptive formation of functional placental tissue.

Glucose metabolism: key endogenous regulator of ß-cell replication and survival.

Recent studies in mice have shown that pancreatic ß-cells have a significant potential for regeneration, suggesting that regenerative therapy for diabetes is feasible. Genetic lineage tracing studies indicate that ß-cell regeneration is based on the replication of fully differentiated, insulin-positive ß-cells. Thus, a major challenge for this field is to identify and enhance the molecular pathways that control ß-cell replication and mass. We review evidence, from human genetics and mouse models, that glucose is a major signal for ß-cell replication. The mitogenic effect of blood glucose is transmitted via glucose metabolism within ß-cells, and through a signalling cascade that resembles the pathway for glucose-stimulated insulin secretion. We introduce the concept that the individual ß-cell workload, defined as the amount of insulin that an individual ß-cell must secrete to maintain euglycaemia, is the primary determinant of replication, survival and mass. We also propose that a cell-autonomous pathway, similar to that regulating replication, appears to be responsible for at least some of the toxic effects of glucose on ß-cells. Understanding and uncoupling the mitogenic and toxic effects of glucose metabolism on ß-cells may allow for the development of effective regenerative therapies for diabetes.

Determinants of pancreatic beta-cell regeneration.

Recent studies have revealed a surprising plasticity of pancreatic beta-cell mass. beta-cell mass is now recognized to increase and decrease in response to physiological demand, for example during pregnancy and in insulin-resistant states. Moreover, we and others have shown that mice recover spontaneously from diabetes induced by killing of 70-80% of beta-cells, by beta-cell regeneration. The major cellular source for new beta-cells following specific ablation, as well as during normal homeostatic maintenance of adult beta-cells, is proliferation of differentiated beta-cells. More recently, it was shown that one form of severe pancreatic injury, ligation of the main pancreatic duct, activates a population of embryonic-type endocrine progenitor cells, which can differentiate into new beta-cells. The molecular triggers for enhanced beta-cell proliferation during recovery from diabetes and for activation of embryonic-type endocrine progenitors remain unknown and represent key challenges for future research. Taken together, recent data suggest that regenerative therapy for diabetes may be a realistic goal.

Disseminated mycobacterial disease caused by Mycobacterium szulgai.

Disseminated mycobacterial disease due to Mycobacterium szulgai occurred in a previously healthy young man. The clinical picture included fever, mediastinal and generalized lymphadenopathy, hemoptysis, and skin lesions but was dominated by progressive multifocal osteomyelitis. Immunological studies revealed a decrease in T-lymphocyte reaction to mitogens, but this was tested late in the course of the disease and may have been secondary. In spite of repeated surgical drainage and treatment with multiple antituberculous drugs for a period of two years, new lesions continue to appear mainly in the bones. Mycobacterium szulgai was isolated from 28 bone specimens, as well as from skin lesions and sputum. To the best of our knowledge, this is the first report of disseminated disease due to this organism.

The efficacy of naltrexone in preventing reabuse of heroin after detoxification.

The efficacy of Naltrexone in preventing reabuse of heroin among heroin addicts in Israel was studied in a double-blind, controlled design. Naltrexone (or placebo) treatment was given as part of a general treatment plan that continued for 12 weeks. Thirty-two addicts who successfully completed a detoxification program and met research criteria, were included in the study. Fifty milligrams of Naltrexone were taken orally three times a week (25 mg twice a week for the first 2 weeks). The follow-up procedure included an interview, urine tests, and screening for possible adverse effects. In addition, social and psychological parameters were evaluated. Fewer heroin-positive urine tests were found the Naltrexone group than in the placebo group. Throughout the entire study, the number of drug-free patients in the Naltrexone group was higher than in the placebo group. The Naltrexone group showed a significant improvement in most psychological parameters as compared with the placebo group. No differences were found in compliance or ratio of adverse effects between the Naltrexone and placebo groups. The concept "heroin abuse load" based on daily heroin consumption and duration of addiction enabled us to predict which addicts would complete the treatment program. The results suggest that heroin addicts in Israel may benefit from treatment with Naltrexone.

Selective role of glutathione in protecting human neuronal cells from dopamine-induced apoptosis.

The role of glutathione and other antioxidants in dopamine-induced apoptosis has been analyzed in cultures of the human neuronal cell line NMB. Apoptosis, induced by 0.1-0.3 mM dopamine, was blocked by glutathione in a dose- and time-dependent manner. This was observed by monitoring cell morphology, cell viability, and the release of the cytosolic enzyme lactate dehydrogenase into the culture medium. L-Cysteine and N-acetylcysteine had a similar effect in protecting against dopamine neurotoxicity, but at lower concentrations than glutathione. The dopamine-induced alteration in the cell cycle profile, detected by flow cytometry (FACS), and intranucleosomal DNA fragmentation, were both blocked by glutathione. Treatment of NMB cells with buthionine sulfoximine, an irreversible inhibitor of gamma-glutamylcysteine synthetase, increased the neurotoxic effect of, dopamine, suggesting that endogenous glutathione participates in reducing dopamine neurotoxicity. The relationship between glutathione and dopamine was further investigated by testing the effect of dopamine on the endogenous glutathione level. Dopamine decreased glutathione levels within 16-24 hr; however, this effect was preceded by a transient increase in the level of the tripeptide within the first 0.5-7 hr. Two other types of endogenous antioxidants, (+)-alpha-tocopherol (vitamin E) and ascorbic acid (vitamin C), were tested; vitamin E (at 1-100 microgram/ml) was inactive against dopamine toxicity, whereas vitamin C had no effect at 0.05-0.2 mM, but increased dopamine toxicity at 0.5-2 mM. The results indicate that glutathione has a selective role in protecting human neural cells from the toxic effect of dopamine. This study may contribute, therefore, to a better understanding of the mechanisms underling the excessive loss of dopaminergic neurons in neurodegenerative diseases, such as Parkinsonism, and in the aging process.

Dopamine-induced apoptosis in human neuronal cells: inhibition by nucleic acids antisense to the dopamine transporter.

Human neuroblastoma NMB cells take up [3H]dopamine in a selective manner indicating that dopamine transporters are responsible for this uptake. These cells were therefore used as a model to study dopamine neurotoxicity, and to elucidate the role of dopamine transporters in controlling cell death. Treatment with 0.05 0.4 mM dopamine changed cells' morphology within 4 h, accompanied by retraction of processes, shrinkage, apoptosis-like atrophy, accumulation of apoptotic particles, DNA fragmentation and cell death. Cycloheximide inhibited dopamine's effect suggesting that induction of apoptosis by dopamine was dependent upon protein synthesis. Dopamine cytotoxicity, monitored morphologically by flow cytometric analysis, and by lactate dehydrogenase released, was blocked by cocaine but not by the noradrenaline and serotonin uptake blockers desimipramine and imipramine, respectively. Attempting to inhibit dopamine transport and toxicity in a drug-free and highly selective way, three 18-mer dopamine transporter antisense phosphorothioate oligonucleotides (numbers 1, 2 and 3) and a new plasmid vector expressing the entire rat dopamine transporter complementary DNA in the antisense orientation were prepared and tested. Antisense phosphorothioate oligonucleotide 3 inhibited [3H]dopamine uptake in a time- and dose-dependent manner. Likewise, transient transfection of NMB cells with the plasmid expressing dopamine transporter complementary DNA in the antisense orientation partially blocked [3H]dopamine uptake. Antisense phosphorothioate oligonucleotide 3 also decreased, dose-dependently, the toxic effect of dopamine and 6-hydroxydopamine. Western blot analysis with newly prepared anti-human dopamine transporter antibodies showed that antisense phosphorothioate oligonucleotide 3 decreased the transporter protein level. These studies contribute to better understand the mechanism of dopamine-induced apoptosis and neurotoxicity.

Effect of low-dose treatment with selegiline on dopamine transporter (DAT) expression and amphetamine-induced dopamine release in vivo.

1. Chronic treatment with low doses of the selective monoamine oxidase (MAO) type B inhibitors selegiline [(-)-deprenyl] and rasagiline, causes elevation in extracellular level of 3,4-dihydroxyphenylethylamine (dopamine) in the rat striatum in vivo (Lamensdorf et al., 1996). The present study was carried out to determine whether this effect of selegiline could be the result of an inhibition of the high-affinity dopamine neuronal transport process. 2. Changes in activity of the dopamine transporter (DAT) in vivo following selegiline treatment were evaluated indirectly by microdialysis technique in the rat, from the change in striatal dopamine extracellular concentration following systemic amphetamine administration (4 mg kg(-1), i.p.). Striatal levels of the DAT molecule were determined by immunoblotting. Uptake of [3H]-dopamine was determined in synaptosomes from selegiline-treated animals. 3. Amphetamine-induced increase in striatal extracellular dopamine level was attenuated by one day and by chronic (21 days) treatment with selegiline (0.25 mg kg(-1), s.c.). 4. Striatal levels of DAT were elevated after 1 and 21 days treatment with selegiline, but were not affected by clorgyline, rasagiline, nomifensine or amphetamine. 5. The increase in DAT expression, and attenuation of amphetamine-induced dopamine release, were not accompanied by a change in [3H]-dopamine uptake in synaptosomes of selegiline-treated animals. 6. The results suggest that a reversible inhibition of dopamine uptake occurs following chronic low dose selegiline treatment in vivo which may be mediated by an increase in endogenous MAO-B substrates such as 2-phenylethylamine, rather than by the inhibitor molecule or its metabolites. Increased DAT expression appears to be a special property of the selegiline molecule, since it occurs after one low dose of selegiline, and is not seen with other inhibitors of MAO-A or MAO-B. The new DAT molecules formed following selegiline treatment appear not to be functionally active.

Bcl-2 and p53: role in dopamine-induced apoptosis and differentiation.

The fate of a neuron in the developing brain to multiply, differentiate, or die in an apoptotic manner depends on the expression of genes that are involved in regulating the cell cycle. Recent studies determined the involvement of several genes, including cyclin A and B2, in dopamine-induced apoptosis in cultured chick sympathetic neurons. Another gene that plays a role in apoptosis and differentiation of neurons, oligodendrocytes and PC12 cells is p53. It is also known that DNA damage increases p53 levels, triggering repair or apoptosis in response to moderate or severe damage, respectively. NMB cells express active and inducible forms of p53, thus being particularly suitable to analyze the role of this gene in dopamine-induced apoptosis and differentiation. The main observation of this work is that low concentrations of dopamine induce differentiation while high concentrations induce apoptosis, and that concentrations of dopamine that induce apoptosis increased p53 levels. There peak increase in p53 was within 3-6 h, before cell death. Thus, treatment with a high dopamine concentration may result in oxidation products and/or free radicals that heavily damage DNA, thus increasing p53 levels and initiating a cascade of events leading to apoptosis. Lower concentrations of dopamine apparently have a milder damaging effect on the DNA and induce growth arrest and differentiation. In various systems Bcl-2 inhibits cell death, being apoptotic or necrotic. Bcl-2, and other members of the family, such as Bax, are located downstream to p53 in the apoptotic pathway, and they contain negative or positive p53 response elements. Bcl-2 also protects cells by acting as antioxidant. Neuronal differentiation may be accompanied with an increase in Bcl-2, though it was suggested that the role of Bcl-2 in differentiation is less critical than in apoptosis. Herein, Bcl-2 was found to inhibit dopamine neurotoxicity. Whether the expression of Bcl-2 is regulated by different dopamine concentrations, or by dibutyryl-cAMP and DMSO, remains to be determined.

Increased collagenolytic activity in severed and sutured tendons following topical application of exogenous collagen in chickens.

To verify the role of collagenase in reduction of peritendinous adhesion by topical application of exogenous collagen, the flexor tendons of 30 chickens were severed and sutured. Exogenous, native enriched collagen solution (ECS) was introduced in the tendon sheath via a polyethylene catheter. The effect of ECS on collagenolytic activity in the healing tendon was assessed 1, 2, and 3 weeks later both by determining the relative amounts of dialyzable protein and hydroxyproline and by using the collagen film collagenase assay. The results obtained indicated a significant increase in both dialyzable hydroxyproline level and collagenolytic activity in the ECS-treated tendons as compared with the untreated controls. It is suggested that the effect of the topically applied exogenous collagen on increasing the collagenolytic activity may be directly related to previously observed increased gliding capacity of the tendons in the same experimental model.

Erythrocyte (Ca2+ + Mg2+)-ATPase activity and calcium homeostasis in Duchenne muscular dystrophy.

Because the erythrocyte (RBC) in Duchenne's muscular dystrophy (DMD) is thought to be a suitable experimental paradigm for the sarcolemma, the RBC membrane-bound enzyme (Ca2+ + Mg2+)-ATPase has been investigated as to its relevance to abnormalities of calcium metabolism in DMD muscle. In this study, RBC (Ca2+ + Mg2+)-ATPase activity, intracellular calcium and potassium contents and complete hemogram were examined in 10 DMD patients and 16 age-matched controls. (Ca2+ + Mg2+)-ATPase activity was found elevated in the DMD RBC, consistent with reports from previous studies, but no abnormalities in intracellular calcium, potassium or hemograms were detected. It seems that although the (Ca2+ + Mg2+)-ATPase activity is changed, it bears no relevance to calcium homeostasis in DMD RBC. It is inferred that the increase in intramuscular calcium in DMD muscle, which is also found in other neuromuscular diseases, may be a non-specific finding in the diseased muscle and part of the final common pathway leading toward cellular degeneration and death.

Persistent plaque formation in experimental murine brucellosis.

Primary plaque forming cells (PFC) are present in spleens of mice 150 days or more following an infection with Brucella abortus. The development of primary plaques in mice long after antigenic challenge is an uncommon phenomenon, unlike the plaque formation (PF) induced by a non-living antigen. The mechanism of this persistent PF has been now investigated in light of a prolonged persistence of the corresponding antigen in tissues. Living E. coli, inoculated in massive dose into mice, survived in their organs for a brief time, while concomitantly PFC disappeared by day sixteen. Infection with B. abortus, in contrast, induced persistent presence of bacteria in the organs of inoculated mice and stimulated long lasting plaque formation. Only direct plaques were found during all stages of infection. Repeated inoculations of dead B. abortus also induced continuous production of primary plaques, whereas an interval in supply of the antigen resulted in disappearance of PFC. Rifampin (40 mg/kg) eliminated bacteria from the treated mice, which resulted in the disappearance of primary PFC. It seems likely that long lasting PF in B. abortus infected mice is connected with a constant antigenic stimulus operating in the carrier state.

Hydatid disease of the spine causing paraplegia. The combined treatment by surgical drainage and mebendazole: a case report.

Hydatid disease of the spine is a rare disease with a poor prognosis. Paraplegia is a severe complication and has a low chance for recovery. Surgical drainage and decompression has been the treatment of choice although success was limited. Medical treatment with mebendazole was introduced in 1977 for cystic and alveolar Hydatid disease of the liver. In this paper, a case with Hydatid disease with complete paraplegia is presented. He was treated by combined surgical and medical treatment that included several surgical drainages, decompression, and fusion procedures, accompanied by high dose mebendazole for three years. Recovery from the paraplegia was complete except for the persistence of a neurogenic bladder. Neither clinical nor laboratory evidence of activity of the disease existed after six years of follow-up. This case must encourage further clinical trials in such cases, combining surgical treatment with mebendazole.

Improvement of gliding function of flexor tendons by topically applied enriched collagen solution.

The long flexor tendons of the second, third and fourth toes of 94 chickens were cut and sutured. After operation the birds were divided into three groups. To reduce peritendinous adhesions, an aqueous solution of beta-aminopropionitrile (BAPN) was added to a solution of enriched native collagen (ECS) and applied to the cut tendons of one group; untreated controls and controls treated with collagen solution alone comprised the other groups. Chickens from each group were killed one, two, three, four and five weeks after operation. The results were evaluated both biomechanically and biochemically. It was found that the collagen solution alone had the same effect as the treatment with BAPN. It is suggested that the exogenous collagen present at the site of injury binds the collagenase inhibitor released by tendon cells, thus providing enough active collagenase to control the formation of fibrous adhesions. The inefficiency of BAPN in these experiments might have been due to either inadequate dosage or wrong timing, or both.

External fixation or flexible intramedullary nailing for femoral shaft fractures in children. A prospective, randomised study.

We report the outcome of 19 children aged 5.2 to 13.2 years with 20 fractures of the femoral shaft requiring surgery, who were randomly assigned to have external fixation (EF) or flexible intramedullary nailing (FIN) (10 fractures each). The duration of the operation averaged 56 minutes for the EF group with 1.4 minutes of fluoroscopy, compared with 74 minutes and 2.6 minutes, respectively, for the FIN group. The early postoperative course was similar, but the FIN [corrected] group showed much more callus formation. The time to full weight-bearing, full range of movement and return to school were all shorter in the FIN group. The FIN complications included one transitory foot drop and two cases of bursitis at an insertion site. In the EF group there was one refracture, one rotatory malunion requiring remanipulation and two pin-track infections. At an average follow-up of 14 months two patients in the EF group had mild pain, four had quadriceps wasting, one had leg-length discrepancy of over 1 cm, four had malalignment of over 5 degrees, and one had limited hip rotation. In the FIN group, one patient had mild pain and one had quadriceps wasting; there were no length discrepancies, malalignment or limitation of movement. Parents of the FIN group were more satisfied. We recommend the use of flexible intramedullary nailing for fractures of the femoral shaft which require surgery, and reserve external fixation for open or severely comminuted fractures.

Cure of the limp in children with congenital dislocation of the hip and ischaemic necrosis. Fifteen cases treated by trochanteric transfer and contralateral epiphysiodesis.

Fifteen patients who limped and had early fatigue on walking caused by ischaemic necrosis after treatment for congenital dislocation of the hip had distal and lateral transfer of the greater trochanter. Nine of them in whom the predicted leg-length discrepancy was more than 3 cm also had epiphysiodesis of the contralateral leg. At skeletal maturity the limp was eliminated and walking distance was significantly improved in them all. In those who had epiphysiodesis the average leg-length discrepancy was 0.7 cm at maturity. Two of those not treated by epiphysiodesis used a heel raise of 1.5 cm. In seven cases the two operations were performed simultaneously without serious complications. This procedure is recommended at about the age of 12 years.

Fine-needle bone biopsy to diagnose osteomyelitis.

In 30 patients in whom osteomyelitis was suspected fine-needle bone biopsies (FNBB) were taken at the same time as bone was aspirated for bacteriological examination. The diagnosis of osteomyelitis was eventually confirmed in 15 patients; the other 15 had myositis (3), arthritis (3), trauma (2), microgeodic phalangeal syndrome (2), haematoma in a non-ossifying fibroma (1), and Ewing's sarcoma (1). In three patients no pathology was found. The temperature, WBC and ESR at presentation did not help to distinguish osteomyelitis from other conditions. FNBB, however, proved to be a useful additional investigation with a sensitivity for osteomyelitis of 87% and a specificity of 93%.

Ultrasonography of the hip in developmental hip dysplasia.

Ultrasonography of the hip was performed sequentially by two different examiners in 75 infants. The ultrasound strips were reviewed twice by three paediatric orthopaedic surgeons and classified by the Graf method. The intraobserver and interobserver agreement between the interpretations was analysed using simple and weighted kappa coefficients calculated for agreement on the Graf classification and for grouping as normal (types 1A to 2A), and abnormal requiring treatment (types 2B to 4). When examining the same ultrasound strip, intraobserver agreement for the Graf classification was substantial (mean kappa 0.61), but interobserver agreement was only moderate (kappa 0.50). For the grouping into normal and abnormal, the mean kappa value for intraobserver agreement was 0.67 and for interobserver agreement 0.57. Because of the significant differences in agreement between normal and abnormal hips, we analysed a subgroup of those with at least one abnormal interpretation. Intraobserver agreement within this subgroup showed moderate reliability (kappa 0.41), but interobserver agreement was only fair (kappa 0.28). Interpretations of two different strips performed sequentially showed significantly lower agreement with an intraobserver kappa value of 0.29 and an interobserver value of 0.28. In the subgroup with at least one abnormal reading, the intraobserver kappa was 0.09 and the interobserver 0.1. Our findings suggest that both the technique of performing ultrasonography and the interpretation of the image may influence the result.