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Biomedical subjects

S Gould

Publications and source records attributed to S Gould.

At least 19 recordsLinked to original sources

Prenatal diagnosis of coarctation of the aorta improves survival and reduces morbidity.

OBJECTIVE: To investigate whether antenatal diagnosis of coarctation of the aorta results in reduced mortality and improved preoperative haemodynamic stability compared with postnatal diagnosis. DESIGN: Retrospective review of all cases of coarctation of the aorta presenting to a tertiary fetal and neonatal cardiology service from January 1994 to December 1998. METHODS: Prenatal, postnatal, and necropsy records were reviewed to determine survival in the two groups. Markers of preoperative illness severity were recorded, including presence of femoral pulse, collapse, left ventricular function, ductal patency on echocardiography, coagulation status, duration of intensive care unit and total hospital stay, heart rate, respiratory rate, plasma creatinine, plasma potassium, and right upper limb blood pressure. A univarate and multivariate analysis was conducted on all variables and a cumulative score was created and subjected to logistic regression analysis. RESULTS: Both collapse and death were more common in the postnatally diagnosed group (p < 0.05). Femoral pulses were more likely to be palpable and there was echocardiographic evidence of duct patency in the antenatally diagnosed infants (p < 0.001 and p < 0.05, respectively). An increased respiratory rate was associated with postnatal presentation (p < 0.05). Infants with haemodynamic instability preoperatively were more likely to have been diagnosed postnatally (p < 0.01). CONCLUSIONS: Antenatal diagnosis of coarctation of the aorta is associated with improved survival and preoperative clinical condition.

Adolescent↗

Detection of the PAX3-FKHR fusion gene in paediatric rhabdomyosarcoma: a reproducible predictor of outcome?

Rhabdomyosarcoma has 2 major histological subtypes, embryonal and alveolar. Alveolar histology is associated with the fusion genes PAX3-FKHR and PAX7-FKHR. Definition of alveolar has been complicated by changes in terminology and subjectivity. It is currently unclear whether adverse clinical behaviour is better predicted by the presence of these fusion genes or by alveolar histology. We have determined the presence of the PAX3/7-FKHR fusion genes in 91 primary rhabdomyosarcoma tumours using a combination of classical cytogenetics, FISH and RT-PCR, with a view to determining the clinical characteristics of tumours with and without the characteristic translocations. There were 37 patients with t(2;13)/PAX3-FKHR, 8 with t(1;13) PAX7-FKHR and 46 with neither translocation. One or other of the characteristic translocations was found in 31/38 (82%) of alveolar cases. Univariate survival analysis revealed the presence of the translocation t(2;13)/PAX3-FKHR to be an adverse prognostic factor. With the difficulties in morphological diagnosis of alveolar rhabdomyosarcoma on increasingly used small needle biopsy specimens, these data suggest that molecular analysis for PAX3-FKHR will be a clinically useful tool in treatment stratification in the future. This hypothesis requires testing in a prospective study. Variant t(1;13)/PAX7-FKHR appears biologically different, occurring in younger patients with more localised disease.

Adolescent↗

Phenobarbitone-induced liver response in wild type and in p53 deficient mice.

The tumour suppressor protein, p53, is involved in the regulation of apoptosis and growth arrest following DNA damage. Mutations of the p53 gene are found in 50-55% of all human cancers (Hollstein et al. Nucl. Acid Res. 22 (1994) 3551), including hepatocellular carcinomas. Phenobarbitone (PB) is a non-genotoxic hepatocarcinogen in rats and mice. With commercial availability of mice where one or both alleles of p53 have been removed we have examined the effect of PB in wild type C57BL/6J mice (p53 +/+), and p53 deficient mice (+/- and -/- p53) to determine whether p53 plays a role in the PB induced liver response. In each strain of mice, chronic administration caused liver enlargement, which was associated with centrilobular hepatocyte hypertrophy and a transient hyperplasia. In addition, an increase in centrilobular epidermal growth factor receptor and its ligand, transforming growth factor alpha and a decrease in mannose-6-phosphate receptor and its mitoinhibitory ligand, TGFbeta1 was also observed immunohistochemically. The similar response in all three strains indicates that p53 probably plays no role in the early PB induced liver effects of hypertrophy and changes in growth factor expression.

Animals↗

Phenobarbitone-induced ploidy changes in liver occur independently of p53.

Liver polyploidisation, characterised by accumulation of tetraploid and octaploid cells, is found with increasing age and after administration of various drugs. The significance and mechanisms controlling polyploidisation are not understood but p53 is a candidate gene to be involved. We have investigated the effect of p53 on sodium phenobarbitone (PB)-induced liver proliferation and polyploidisation. Using p53 wild type (+/+), heterozygous (+/-) and homozygous (-/-) C57BL/6J mice, we measured ploidy and proliferation (BrdU incorporation) after 21 days oral administration of PB. Administration of PB caused a striking ploidy change compared with untreated controls, with an increase in 8n cells, and no difference noted comparing the p53 genotypes. BrdU positivity also increased significantly compared with controls, with the increase in BrdU positivity occurring in 8n cells. Our results confirm that PB is a hepatic mitogen that causes liver polyploidisation with a striking increase in 8n cells within the liver. p53 status does not appear to have any effect on this PB-induced ploidy change.

Animals↗

PAX3-FKHR induces morphological change and enhances cellular proliferation and invasion in rhabdomyosarcoma.

Alveolar rhabdomyosarcoma (ARMS) is consistently associated with the characteristic translocations t(2;13)(q35;q14) and t(1;13)(p36;q14), which encode for the PAX3-FKHR and PAX7-FKHR fusion oncoproteins respectively. We have investigated the relationship between PAX3-FKHR expression and ARMS histogenesis in primary tumors and cell culture systems. In a blinded histological review of discrepant primary tumors in which there was PAX3-FKHR expression but embryonal histology, we found small areas of alveolar histology in 6 of 11 cases. This suggests that histology alone may under-represent the association between PAX3-FKHR and ARMS, and we investigated this link by examining the effect of ectopic PAX3-FKHR expression on RMS cells. Two cell lines, RD and HX170C, were stably transfected with a PAX3-FKHR expression construct. In cloned transfectants derived from both lines, PAX3-FKHR expression resulted in increased proliferative rate in vitro and promoted cell growth in the absence of added growth factors. Tumors that formed as xenografts in immunodeficient mice were faster growing, more locally invasive, and had a denser, more pleomorphic architecture than untransfected or empty vector transfected tumors. The characteristic clefts and alveolar spaces of ARMS, however, were not seen. In contrast, tumors grown as xenografts from individual clones derived from ARMS cell lines showed all of the classical morphological features of ARMS suggesting divergence in vivo from precursor cells propagated in culture.

Animals↗

Functional results two years after laparoscopic rectopexy.

BACKGROUND: Rectopexy is one of the accepted treatment options for full-thickness rectal prolapse, but the details of the technique remain controversial. This unit has adopted a laparoscopic approach as an alternative to open surgery, and has used three techniques: mesh, suture, and resection. This retrospective study compares the long-term outcome. METHODS: From 1993 to 1995, 14 patients underwent a laparoscopic posterior mesh rectopexy. From 1996 to 1999, 34 patients underwent laparoscopic suture rectopexy with (n = 18) or without sigmoid resection (n = 16). RESULTS: There was no postoperative mortality, and morbidity was similar in the three groups, ranging from 11 to 19%. The mean follow-up was 47, 24, and 20 months for mesh, suture, and resection rectopexy, respectively. During follow-up, 1 patient in each group developed mucosal prolapse. There was no difference between the three groups for incontinence rate, which improved in more than 75% of patients who had impaired continence preoperatively. Postoperative constipation was observed in 2 patients (11%) after resection rectopexy, in 10 (62%) after suture rectopexy (P < 0.01 versus resection), and in 9 (64%) after mesh rectopexy (P < 0.01 versus resection). CONCLUSIONS: Our results show that the addition of sigmoid resection to laparoscopic rectopexy is safe and could contribute to reduce the risk of severe constipation after operation. Laparoscopic mesh rectopexy confers no advantage over the sutured technique, which we now use as our fixation method of choice.

Aged↗

Circumcision: we have heard from the experts; now let's hear from the parents.

OBJECTIVE: The current study sought to investigate parental attitudes about circumcision and their satisfaction with the decision. METHODOLOGY: Parents of boys (6 months to 36 months old) in 3 different practices filled out a questionnaire while waiting for their child's well-child examination. RESULTS: A total of 149 families were surveyed. Families (68) who did not have their sons circumcised were less satisfied with their decision. Compared with families (81) of circumcised children, parents of uncircumcised boys were less likely to have been asked by their physician about whether they wanted their child circumcised, believed that they did not receive adequate information about the procedure, felt less respected by their medical provider, and were more likely to reconsider their decision. CONCLUSION: The importance of adequate information and discussion is highlighted by this study.

Attitude to Health↗

Evaluating a problem based learning course: an action research study.

Problem based learning (PBL) has been widely used in the United States, United Kingdom and Australasia in undergraduate nursing education to develop critical thinking and problem solving skills. PBL has been used since 1996 in a Bachelor of Nursing course at a New Zealand tertiary institution, and several modifications have been made to foster effective learning. The 'pure' PBL process has been adapted to move students gradually from teacher direction to taking responsibility for their learning. This has provided the opportunity for students to develop critical thinking, problem solving, information retrieval and evaluation skills, and group process skills over an 18-week period. Because rigorous evaluation of these changes had not been formally undertaken, the purpose of this study was to evaluate how the current format was developing students' understanding and integration of knowledge. Two cycles of the action research method (Cardno and Piggot-Irvine, 1994) were used, involving 4 lecturers and 17 students. Data was collected both quantitatively and qualitatively over a 16-week period. Findings indicated the importance of: explaining the purpose and process of PBL; communicating in detail the role of both students and lecturers; keeping communication lines open; addressing timetabling issues and valuing this method of learning for nursing practice. Implications for nursing education are addressed.

Health Services Research↗

[Transanal endoscopic microsurgery: a forgotten minimally invasive technique].

OBJECTIVES: The aim of this study was to evaluate transanal endoscopic microsurgery in patients with benign and malignant rectal tumours with special reference to feasibility, morbidity, and recurrence rate. METHODS: Forty-three patients underwent transanal endoscopic microsurgical excision of rectal tumours between 1996 and 2000. The histological diagnosis was benign adenoma in 30 and invasive carcinoma in 13. The mean height of the tumour above the anal verge was 11.2 +/- 3 cm and the mean diameter of the lesion was 3.4 +/- 1.5 cm. RESULTS: The mean operative time was 85 +/- 26 min and in one case (2%), it was necessary to convert to an anterior resection. The morbidity rate was 18%. Mean hospital stay was 3.9 +/- 2.4 days. Complete excision of the tumour with histological confirmation was achieved in 42 cases (98%). With a mean follow-up of 26 months, benign tumour recurrence was observed in one patient (3%). Of the 13 patients with carcinoma, two had immediate further radical resection. For the remaining 11 patients, with a mean follow-up of 19 months, the recurrence rate was 75% for T2 tumours and nil for T1 tumours. CONCLUSIONS: Transanal endoscopic microsurgery is safe and feasible technique which should have a useful place in the management of sessile adenomas of the mid and upper rectum. Its role in the management of rectal cancer is limited, although it may be appropriate for carefully selected cases.

Adenoma↗

Changing pattern of expression of parvalbumin immunoreactivity during human fetal spinal cord development.

Expression of the calcium binding protein parvalbumin (PV) by different classes of spinal neuron has been shown to be developmentally regulated in both rat and monkey. From postmortem studies of eight human cervical spinal cords ranging in age from 11 to 35 weeks postconceptional age, we report that parvalbumin immunoreactivity is similarly plastic in human lower cervical spinal cord development, with many changes occurring prenatally. At 11-14 weeks postconceptional age, there was prominent immunostaining of primary sensory afferents that could be seen coursing through the dorsal horn and extensively innervating the motoneuron pools. Motoneurons were also found to be clearly immunoreactive for choline acetyltransferase by this age. A few ventral horn neurons that were not motoneurons were also parvalbumin immunoreactive. By 24-27 weeks postconceptional age, sensory afferents were still immunoreactive, as were many other axons throughout the white matter. In addition, many ventral horn neurons were now immunoreactive as well as a few dorsal horn neurons. By 31-35 weeks postconceptional age, there was extensive immunostaining of neurons throughout the spinal cord, including a few moderately immunoreactive motoneurons. There were many immunopositive axons in all the white matter tracts except the corticospinal tracts; however, staining of sensory axons traversing the grey matter was less prominent by this age. In the rat, expression of PV by primary sensory neurons coincides with the onset of fetal limb movement. The onset of expression of PV in ventral horn neurons coincides with later developmental events after the arrival of corticospinal inputs, whereas widespread PV immunoreactivity in dorsal horn neurons marks the attainment of a mature pattern of PV expression. The extent to which expression of PV immunoreactivity can be taken to indicate landmarks in human development will be discussed.

Age Factors↗

Chronic deciduitis in the placental basal plate: definition and interobserver reliability.

This study tested whether concordance could be achieved for abnormal inflammation in the basal decidua of placental specimens among 6 pathologists experienced in placental pathology. Thirty microscope slides were evaluated by the pathologists for chronic deciduitis. They also scored the severity and extent of inflammation and the presence of plasma cells. No definition of chronic deciduitis was provided. Concordance (5/6 or 6/6 agreement) was achieved in 23 cases (76%). Spearman's rank correlation showed that the diagnosis of chronic deciduitis was almost identical to the assessment of the severity of the inflammation. A regression analysis showed that the perception of severity (and hence chronic deciduitis) was influenced by the other 2 variables, extent and plasma cells. The results were shared with the pathologists, and 25 cases (excluding those with previous 6/6 consensus) were reevaluated. Concordance was now achieved in the 83% of those remaining cases. Using a threshold based on the severity and the extent of lymphocytes, and the presence of plasma cells, pathologists are able to diagnose chronic deciduitis with sufficient concordance to be of value in clinical correlation studies.

Adult↗

Five cases of brain injury following amniocentesis in mid-term pregnancy.

This paper describes the neuroimaging and neuropathological findings in five cases of severe brain damage after traumatic mid-trimester amniocentesis, all performed between 1986 and 1994. Although fetal injury after amniocentesis has been reported, reports of brain injury are infrequent. Continuous ultrasound monitoring may reduce the risk of fetal injury but follow-up ultrasound scans can be falsely reassuring. Withdrawal of blood-stained fluid, particularly if it contains tissue fragments, should alert the operator to the possibility of fetal damage. Histological examination of such tissue fragments may confirm the nature of the fetal damage. The consequences of fetal brain injury are severe, all five of our cases showed evidence of disruption of brain development compatible with mid-term injury. Obstetricians and their patients should be aware of the small but significant risk of brain damage after mid-term amniocentesis.

Adult↗

Association of primary Pneumocystis carinii infection and sudden infant death syndrome.

To delineate clinical and histological features of the first Pneumocystis carinii infection affecting the immunocompetent host, P. carinii-specific histological stains were performed on autopsy lung specimens from 534 consecutive pediatric patients (those with AIDS and malignancies were excluded) in Santiago, Chile. P. carinii clusters were found in 4 (25%) of 16 infants who died of no apparent cause at arrival to the emergency department, and in 10 (2.9%) of 342 infants who died of multiple conditions at the hospital (P=.002, Fisher's exact test). This prompted us to analyze additional series of infants with sudden infant death syndrome (SIDS). In 161 additional SIDS cases, 47 (35.1%) of 134 infants from Chile and 4 (14.8%) of 27 infants from Oxford, United Kingdom, were found to have P. carinii clusters in the lungs. The quantity of P. carinii cysts was small compared with the numbers seen in immunocompromised hosts with P. carinii pneumonitis. This study provides histological evidence that primary P. carinii infection is associated with SIDS.

Autopsy↗

Magnetic resonance guided general surgery.

Image guided surgery can be defined as the intraoperative use of a radiologicai technique to give the surgeon information not available from direct inspection or palpation of the surgical field. This information may then be used to change the course of an operative procedure. Magnetic resonance (MR) imaging has the potential to be the most useful radiologicai technique in the developing field of image guided surgery.

Journal Article↗

Late-onset deep prosthetic infection following mesh repair of inguinal hernia.

BACKGROUND: The use of prosthetic biomaterials for the primary repair of inguinal hernias is now commonplace. Late-onset deep-seated prosthetic infection can be an unexpected complication. METHODS: The literature from a Medline search relating to the biology of mesh in the setting of hernia repair is discussed. CONCLUSIONS: The use of a foreign body for hernia repair does not appear to alter the incidence of superficial wound infection. Late-onset deep graft infection has been rarely reported, and the true incidence is yet to be established. With the more widespread use of mesh materials, this complication may become increasingly evident.

Anti-Bacterial Agents↗

Outcome of prenatally diagnosed anterior abdominal wall defects.

One hundred consecutive cases of confirmed anterior abdominal wall defect, identified prenatally in the Oxford Prenatal Diagnosis Unit over 11 years, were studied. Fifty nine per cent of cases were suspected omphaloceles and 41% suspected gastroschisis. Fifty four per cent of omphaloceles were accompanied by other defects compared with 5% of those with gastroschisis. Overall, 29% of fetuses with omphalocele had an abnormal karyotype, and of those with another abnormality identified on scan (excluding four cases with no karyotype performed), 54% had an abnormal karyotype. Of the 27 cases with suspected isolated omphalocele, 14 were live born, all of whom have survived. If the 11 whose parents opted for termination of pregnancy are excluded, survival to birth was 88%. Six of the suspected isolated omphaloceles have Beckwith Wiedemann syndrome (BWS). Eight (57%) of the live born babies with omphaloceles had major problems up to the age of 2, but only one (7%) has long term major problems. This child has BWS and is deaf. Of the 39 cases of suspected isolated gastroschisis, 33 (85%) pregnancies resulted in live birth and one in neonatal death after surgery. Survival rate (excluding terminated pregnancies) was 97%. Gastroschisis was associated with a younger maternal age than omphalocele (p < 0.001) and lower birthweight centile (p < 0.01). Fifteen per cent of the gastroschisis babies had major problems up to the age of 2 years and 12% long term developmental problems. Ninety three per cent of the omphalocele babies and 88% of those who had gastroschisis have no long term problems. Over the study period there have been major changes in scanning equipment and expertise. Since 1991 no woman with a suspected isolated lesion has opted for termination of pregnancy.

Abnormalities, Multiple↗