Elective delivery at 34 weeks vs routine obstetric care in fetal gastroschisis: randomized controlled trial.

OBJECTIVE: To evaluate whether elective preterm delivery (ED) at 34 weeks is of postnatal benefit to infants with isolated gastroschisis compared with routine obstetric care (RC). METHODS: Between May 2013 and September 2015, all women with a sonographic diagnosis of fetal gastroschisis referred to a single tertiary center, before 34 weeks' gestation, were invited to participate in this study. Eligible patients were randomized to ED (induction of labor at 34 weeks) or RC (spontaneous labor or delivery by 37-38 weeks, based on standard obstetric indications). The primary outcome measure was length of time on total parenteral nutrition (TPN). Secondary outcomes were time to closure of gastroschisis and length of stay in hospital. Outcome variables were compared using appropriate statistical methods. Analysis was based on intention-to-treat. RESULTS: Twenty-five women were assessed for eligibility, of whom 21 (84%; 95% CI, 63.9-95.5%) agreed to participate in the study; of these, 10 were randomized to ED and 11 to RC. The trial was stopped at the first planned interim analysis due to patient safety concerns and for futility; thus, only 21 of the expected 86 patients (24.4%; 95% CI, 15.8-34.9%) were enrolled. Median gestational age at delivery was 34.3 (range, 34-36) weeks in the ED group and 36.7 (range, 27-38) weeks in the RC group. One patient in the ED group delivered at 36 weeks following unsuccessful induction at 34 weeks. Neonates of women who underwent ED, compared to those in the RC group, showed no difference in the median number of days on TPN (54 (range, 17-248) vs 21 (range, 9-465) days; P = 0.08), number of days to closure of gastroschisis (7 (range, 0-15) vs 5 (range, 0-8) days; P = 0.28) and length of stay in hospital (70.5 (range, 22-137) vs 31 (range, 19-186) days; P = 0.15). However, neonates in the ED group were significantly more likely to experience late-onset sepsis compared with those in the RC group (40% (95% CI, 12.2-73.8%) vs 0%; P = 0.03). CONCLUSION: This study demonstrates no benefit of ED of fetuses with gastroschisis when postnatal gastroschisis management is similar to that used in routine care. Rather, the data suggest that ED is detrimental to infants with gastroschisis. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Parto inducido a las 34 semanas versus atención obstétrica rutinaria en la gastrosquisis fetal: ensayo controlado aleatorizado OBJETIVO: Evaluar si el parto pretérmino inducido (PI) a las 34 semanas es beneficioso para los recién nacidos con gastrosquisis aislada en comparación con la atención obstétrica rutinaria (AR). MÉTODOS: Entre mayo de 2013 y septiembre de 2015, se invitó a participar en este estudio a todas las mujeres con diagnóstico ecográfico de gastrosquisis fetal remitidas a un mismo centro terciario, antes de las 34 semanas de gestación. Las pacientes elegibles fueron asignadas al azar al PI (inducción del parto a las 34 semanas) o a la AR (parto espontáneo a las 37-38 semanas, en función de los indicios obstétricos estándar). La medida de resultado primaria fue la duración de la nutrición parenteral total (NPT). Las medidas de resultado secundarias fueron el tiempo hasta el cierre de la gastrosquisis y la duración de la estancia hospitalaria. Las variables de resultado se compararon mediante métodos estadísticos apropiados. El análisis se basó en la intención de tratar. RESULTADOS: Se evaluó la elegibilidad de 25 mujeres, de las cuales 21 (84%; IC 95%, 63,9-95,5%) aceptaron participar en el estudio; de ellas, 10 fueron asignadas al azar al PI y 11 a la AR. El ensayo se detuvo después del primer análisis provisional planificado debido a preocupaciones sobre la seguridad de las pacientes y por su intrascendencia; por lo tanto, sólo se reclutaron 21 de las 86 pacientes esperadas (24,4%; IC 95%, 15,8-34,9%). La mediana de la edad gestacional en el momento del parto fue de 34,3 (rango: 34-36) semanas en el grupo de PI y 36,7 (rango: 27-38) semanas en el grupo de AR. Una paciente del grupo de PI tuvo un parto a las 36 semanas, después de una inducción infructuosa a las 34 semanas. Los neonatos de las mujeres que se sometieron a PI, comparados con los del grupo de AR, no mostraron diferencias en la mediana del número de días de NPT (54 (rango: 17-248) vs 21 (rango: 9-465) días; P=0,08), número de días hasta el cierre de la gastrosquisis (7 (rango: 0-15) vs 5 (rango: 0-8) días; P=0,28) y duración de la estancia hospitalaria (70,5 (rango: 22-137) vs 31 (rango: 19-186) días; P=0,15). Sin embargo, la probabilidad de experimentar sepsis de inicio tardío fue mayor en los neonatos del grupo de PI en comparación el grupo de AR (40% (IC 95%, 12,2-73,8%) vs 0%; P=0,03). CONCLUSIÓN: Este estudio demuestra que el PI no presenta ningún beneficio para los fetos con gastrosquisis cuando el tratamiento de la gastrosquisis postnatal es similar al utilizado en la atención rutinaria. Más bien, los datos sugieren que el PI es perjudicial para los lactantes con gastrosquisis.

Size of common bile duct stones on MRCP predicts likelihood of positive findings at ERCP.

OBJECTIVE: To ascertain if direct measurement of the size of common bile duct stones (CBD) on magnetic resonance cholangio-pancreatography (MRCP) can be used to predict the likelihood of a positive endoscopic retrograde cholangio-pancreatography (ERCP) result. Should we be carrying out ERCPs on all patients with CBD stones? METHODS: We retrospectively analysed the records of 1812 consecutive patients undergoing MRCP between November 2009 and November 2014 at the Victoria Infirmary. A measurable CBD stone was present in 383 patients, of whom 293 successfully underwent ERCP. RESULTS: 221 patients (75%) had stones demonstrated on ERCP. A receiver operating curve (ROC) was plotted correlating stone size with the likelihood of a positive ERCP result, and demonstrates that using a cut off of >4 mm as an indication for ERCP gives the mathematical best-fit correlation with a sensitivity of 83% (95% CI 78-88) and specificity of 66% (95% CI 53-77). CONCLUSIONS: In our current practice, all patients with CBD stones at MRCP are considered for ERCP regardless of stone size. Our results would support the hypothesis that as size decreases the likelihood of spontaneous stone passage increases. Although the threshold of mathematical best compromise is >4 mm to minimise both type 1 and type 2 errors, we would favour a lower threshold of 2 mm above which ERCP is performed (sensitivity 98.65, 95% CI 96.1-99.7, specificity 25.71%, CI 16.0-37.6). For patients with stones measuring 2 mm or less, early operative intervention with intraoperative cholangiography to confirm duct clearance could be a suitable alternative.

Successful use of albuterol in a patient with central core disease and mitochondrial dysfunction.

Albuterol, a selective beta-adrenergic agonist, has been used experimentally in combination with exercise therapy in a few inherited neuromuscular disorders to increase muscle strength and muscle volume . We report on a 9-year-old boy with central core disease and mitochondrial dysfunction due to compound heterozygous RYR1 mutations receiving albuterol treatment for 1 year. Throughout the period of albuterol administration, the patient underwent an aerobic exercise regime of training sessions three times a week that lasted 20 min each. No side effects of albuterol use were seen. Significant clinical progress, including self care, sitting up, raising arms above the shoulders, independent feeding, and better speech and writing were observed compared with minimal development of these abilities in the previous years on physiotherapy. Improved forced expiratory volume in 1 s (FEV1) score was detected and increased muscle strength was noted: progress was measured using various functional tests and assessment scales. The only complication observed was a mild progression of the joint contractures, possibly due to an unbalance between the flexor and extensor musculature. In general, in this pilot study in a complex case of metabolic myopathy our patient has shown promising results following albuterol treatment and aerobic exercise therapy.

Premature termination of tubulin gene transcription in Xenopus oocytes is due to promoter-dependent disruption of elongation.

We have shown previously that the Xenopus alpha-tubulin gene, X alpha T14, exhibits premature termination of transcription when injected into oocyte nuclei. The 3' ends of prematurely terminated transcripts are formed immediately downstream of a stem-loop sequence found in the first 41 bp of the 5' leader. We show here, using deleted constructs, that premature termination requires the presence only of sequences from -200 to +19 relative to the initiation site. Deletion of the stem-loop does not increase the production of extended transcripts, and premature termination apparently continues at nonspecific sites. This finding indicates that disruption of the elongation phase of transcription rather than abrogation of a specific antitermination mechanism is the cause of premature termination in X alpha T14. We also found that disruption of elongation on a reporter gene could be induced specifically by competition with X alpha T14 promoters. To identify which elements of the promoter might interact with elongation determinants to cause this competition, we constructed a series of internal promoter mutants. Most mutations in the -200 to -60 region of the promoter had some effect on initiation frequency but did not cause any significant change in levels of premature termination. However, mutations in the core promoter that removed the TATA box consensus causes major change in initiation and resulted in a marked decrease in the production of prematurely terminated transcripts relative to extended transcripts. We discuss why such promoters can apparently escape the disruption of elongation that leads to premature termination.

Molecular characterization of a zebrafish TCF ETS-domain transcription factor.

The ternary complex factor (TCF) subfamily of ETS-transcription factors represent key nuclear targets of the MAP kinase pathways. Members of this subfamily are classified by the presence of several conserved domains for DNA binding, interaction with SRF, interaction with MAP kinases and transcriptional activation. In this study we have isolated a further member of this subfamily (TCF-1) from zebrafish. The protein product of zebrafish TCF-1 (zTCF-1), shares sequence similarity with the mammalian TCFs in all four conserved domains, with highest overall similarity to SAP-1. Zebrafish TCF-1 is expressed throughout zebrafish embryonic development and exhibits typical TCF DNA binding characteristics, with the B-box being required for interaction with SRF. Of the mammalian TCFs, its DNA binding specificity resembles Elk-1. zTCF-1 is a target for both the growth factor/mitogen-activated and stress-activated MAP kinase cascades in vitro and in vivo. However, differential targeting occurs, with the profile of its activation closely resembling that of mammalian SAP-1. Together, our results demonstrate that the TCFs have been functionally conserved during vertebrate development.

Acquired abnormalities of the biliary tract from chronic gallstone disease.

BACKGROUND: Acquired abnormalities of the biliary tract from chronic gallstone disease are rare. The aim of this study was to examine the frequency with which these abnormalities occur and to assess the probability of encountering such an abnormality at laparoscopic cholecystectomy. STUDY DESIGN: We conducted a prospective study of all patients undergoing elective and emergency cholecystectomy under the care of one surgeon between January 1991 and December 1997. RESULTS: Biliary tract abnormalities from chronic gallstone disease were encountered in 10 (2%) of 486 patients undergoing cholecystectomy. Four were observed in patients undergoing elective laparoscopy cholecystectomy, and the remainder were observed at open cholecystectomy. Five had a cholecystocholedochal fistula (Mirizzi Syndrome Type II), and one had a stone impacted at the cystic duct-bile duct junction (Mirizzi Syndrome Type I). Two had cholecystoduodenal fistulas and two had an absent cystic duct with a normal bile duct. Both instances of an absent cystic duct were encountered at laparoscopic cholecystectomy; in one the bile duct was mistaken for the cystic duct and a 2-cm segment was excised at operation, and in the other the abnormality was recognized and confirmed by cholangiography. CONCLUSIONS: This study demonstrates a similar incidence of acquired abnormalities of the biliary tract from chronic gallstone disease to that already reported. But acquired absence of the cystic duct may occur more frequently than previously suspected. Patients with this condition are at high risk for bile duct injury during laparoscopic cholecystectomy. Clinical awareness of this problem with strict adherence to the principles taught at open cholecystectomy may prevent or reduce the severity of bile duct injury in these patients.

What effect does the duration of an inguinal hernia have on patient symptoms?

BACKGROUND: Despite the fact that repair of an inguinal hernia is one of the most common operations performed in general surgery, we have very little information on the natural history of the untreated hernia. The aim of this study was to evaluate the association between hernia symptoms and the duration the patients had their hernias before presentation to a surgical outpatient department for an elective or emergency operation. STUDY DESIGN: Data were gathered prospectively on a consecutive series of 699 patients admitted to two University Departments of Surgery for scheduled operations for an inguinal hernia. RESULTS: More than one third (267) of patients had their hernias for 1 year or longer, up to 65 years, before presentation. The most common symptom on presentation was pain or discomfort at the hernia site, which occurred in 457 (66%) patients. The cumulative probability of pain increased with time to almost 90% at 10 years. The hernia had become irreducible in 48 patients (6.9%). The cumulative probability of irreducibility increased from 6.5% (95% confidence interval 4% to 9%) at 12 months to 30% (95% confidence interval 18% to 42%) at 10 years. Leisure activities were affected in 29% of patients although only 13% of patients had to take time off work because of hernia-related symptoms. Only two patients (0.3%) required resection of infarcted bowel or omentum. CONCLUSIONS: Because many patients with an inguinal hernia are asymptomatic or mildly symptomatic, prospective clinical trials to assess the role of operations for such hernias are required.

Does contraction of mesh following tension free hernioplasty effect testicular or femoral vessel blood flow?

Prosthetic mesh can contract by 20-75% of its original size within ten months after implantation. We set out to determine whether this contraction has any effect on testicular or femoral vessel blood flow following open or laparoscopic hernia repair. Twenty patients who underwent mesh repair of a primary unilateral inguinal hernia repair by Open (10) or Laparoscopic (10) methods a median of 3 years previously were investigated by ultrasound to determine the haemodynamic characteristics of the testis and femoral vessels. There was no significant difference in testicular blood flow, volume or echogenicity between the different types of repair or the contralateral side. The vertical and transverse dimensions of the femoral artery and vein were similar in all groups as was blood flow. Mesh contraction following inguinal hernioplasty does not adversely affect the testis or femoral vessels and can be used safely for both anterior and preperitoneal approaches.

[Changes in chromatin organization during early development and carcinogenesis]. / Izmeneniia organizatsii khromatina v rannem razvitii i pri kantserogeneze.

Similar changes in chromatin organization take place during development and carcinogenesis. The size of chromatin loop domains fixed on the nuclear skeleton (matrix) increased from 20 to approximately 200 kbp. These changes are accompanied by an increased size of replicons and altered specificity of loop attachment to the nuclear matrix. During carcinogenesis, inverse changes in the chromatin structure are observed, neoplastic cells are dedifferentiated and return to the initial state. In this review, we consider new experimental data on organization of the DFNA loops and nuclear matrix in embryogenesis and carcinogenesis.

Rearrangement of chromatin domains during development in Xenopus.

A dynamic change in the organization of different gene domains transcribed by RNA polymerase I, II, or III occurs during the progression from quiescent [pre-midblastula transition (pre-MBT)] to active (post-MBT) embryos during Xenopus development. In the rDNA, c-myc, and somatic 5S gene domains, a transition from random to specific anchorage to the nuclear matrix occurs when chromatin domains become active. The keratin gene domain was also randomly associated to the nuclear matrix before MBT, whereas a defined attachment site was found in keratinocytes. In agreement with this specification, ligation-mediated (LM)-PCR genomic footprinting carried out on the subpopulation of 5S domains specifically attached to the matrix reveals the hallmarks of determined chromatin after the midblastula transition. In contrast, the same analysis performed on the total 5S gene population does not reveal specific chromatin organization, validating the use of nuclear matrix fractionation to unveil active chromatin domains. These data provide a means for the determination of active chromosomal territories in the embryo and emphasize the role of nuclear architecture in regulated gene expression during development.

Rearrangement of chromatin domains in cancer and development.

Both the accomplishment of developmental programs and neoplastic transformation are linked to changes in the long-range organization of chromatin, in particular, DNA loop domains. The development of new methods that allow the study of interactions between the bases of DNA loops and the proteins of the nuclear matrix will help our understanding of the molecular mechanisms in such changes. These methods should also allow the establishment of a fingerprint "signature" for many cancers that may serve for diagnostic purposes. J. Cell. Biochem. Suppl. 35:54-60, 2000.

Genes encoding isoforms of transcription elongation factor TFIIS in Xenopus and the use of multiple unusual RNA processing signals.

We have identified cDNAs encoding three related forms of transcription elongation factor TFIIS (S-II) in Xenopus laevis ovary. Comparison of Xenopus and mammalian sequences identifies likely diagnostic amino acids that distinguish classes of vertebrate TFIIS. The diversity of TFIIS polypeptides in Xenopus is due partly to the presence of two diverged genes in this tetraploid genome. We isolated genomic clones containing one of the genes, xTFIIS.oA, and, unlike a previously described vertebrate TFIIS gene, found that it contains introns. Alternative splicing at a CAG/CAG motif containing the 3' splice site of intron 4 produces the third form of xTFIIS, which differs from one of the others simply in lacking Ser109. Intron 6 of xTFIIS.oA contains splice and branch site consensus sequences conforming to those of the minor class of AT-AC introns and this was confirmed for the homeologous xTFIIS.oB gene by genomic PCR. Other unusual but functional variants of RNA processing signals were found in xTFIIS genes at the 5' splice site of intron 8 and the polyadenylation hexanucleotides. Utilization of multiple unusual processing signals may make the generation of mature xTFIIS.o mRNAs inefficient and the possible regulatory consequences of this are discussed.

Control of gene expression in Xenopus early development.

We examine the control of gene expression before and through the MBT in Xenopus laevis. The generalized repression of transcription that occurs before the midblastula transition (MBT) is regulated by a dynamic competition between chromatin and transcription complex assembly. Conditions favoring the access of basal factors (TBP) or transactivators can overcome this transcriptional repression. Changes in DNase I hypersensitivity patterns of the chromatin during early development show that it is more accessible to DNase I before the MBT (and by extension to other DNA interacting proteins) than after the MBT. We also show that at the level of genomic domains, organization of the chromatin matrix attachment sites is random before MBT. We propose that these three components, chromatin domain structure, DNA accessibility, and the transcription complex-chromatin dynamic competition, combine to regulate transcription in the embryo before and through the MBT.

Diagnosis of a femoral hernia in the elective setting.

UNLABELLED: A femoral hernia accounts for approximately 5-10% of all groin hernias in adults. Misdiagnosis in children, in whom the condition is rare, has been well recognised and documented. The aim of this study was to assess the accuracy of diagnosis in an adult population. METHODS: An analysis of 379 patients with a groin hernia, presenting electively to a University Department of Surgery and entered into a prospective clinical trial. RESULTS: A femoral hernia was confirmed at operation in 12 (3%) patients while a further 4 had a preoperative diagnosis of a femoral hernia. The correct diagnosis of a femoral hernia was made in only 3 cases by general practitioners and in only 6 by surgical staff of all grades. CONCLUSION: These data suggest that medical staff of all grades may be poor at diagnosing a femoral hernia and a change in the way we are taught to differentiate between femoral and inguinal hernia needs to be considered.

Pharmaceutical care needs of patients with angina.

OBJECTIVE: The aim of this study was to evaluate patient knowledge and assess the management of angina for patients receiving sublingual glyceryl trinitrate (GTN) METHOD: Prospective data collection and patient interview was undertaken in 17 community pharmacies. RESULTS: During the study 488 angina patients presented to the participating pharmacies. Data were collected for 347 patients receiving sublingual GTN. Problems with administration technique were identified for 108 patients (31%) and knowledge of when to seek medical help appropriately after failed GTN use was unsure for 134 patients (39%) or poor for 88 patients (25%). Eighty five patients (24%) were not receiving regular symptomatic therapy. Aspirin was prescribed or purchased by 253 patients (73%). Seven pharmacies participated in GP referral (data collected for 201 patients); 31 patients (15%) were referred usually with a recommendation to add aspirin. The outcome of 20 of these referrals was assessed; advice was taken for 13 patients, 3 patients failed to attend GP, aspirin was contraindicated for 3 patients and one patient already attended pharmacist medication review. CONCLUSION: This study demonstrated the potential contribution community pharmacists could make at the time of dispensing to the management of patients with angina.

Groin hernia repair in Scotland.

BACKGROUND: The use of mesh for groin hernia repair has dramatically changed the way this common operation is performed. The aim of this study was to survey the methods of groin hernia repair in Scotland and to assess patient satisfaction with the operation. METHODS: Between 1 April 1998 and 31 March 1999 all patients who underwent groin hernia repair in the National Health Service in Scotland were identified. As well as looking at the type of hernia repair performed and postoperative morbidity, patients were sent a Short Form-36 about 3 months after the operation to assess satisfaction and return to normal activity. RESULTS: Information was obtained on 5506 (97 per cent) of patients who underwent groin hernia repair during the study period. Eighty-five per cent of patients had an open mesh repair and 4 per cent had a laparoscopic repair. Most operations (85 per cent) were performed using general anaesthesia on an inpatient basis (78 per cent), and 8 per cent were for repair of a recurrent hernia. Potentially serious intraoperative complications were rare (seven patients), although they were significantly (P < 0. 001) more likely to be associated with a laparoscopic approach or repair of a femoral hernia: relative risk compared with open inguinal hernia repair 33 (95 per cent confidence interval (c.i.) 6-197) and 22 (95 per cent c.i. 3-152) respectively. Wound complications were common and 10 per cent of patients required a district nurse to attend the wound. Patients expressed a high degree of satisfaction; 94 per cent would recommend the same operation to someone else if required. CONCLUSION: An open mesh repair using general anaesthesia has become the repair of choice for a groin hernia in Scotland. Despite a high incidence of wound complications, patients are satisfied with this operation.