Large expansion of the ATTCT pentanucleotide repeat in spinocerebellar ataxia type 10.

Spinocerebellar ataxia type 10 (SCA10; MIM 603516; refs 1,2) is an autosomal dominant disorder characterized by cerebellar ataxia and seizures. The gene SCA10 maps to a 3.8-cM interval on human chromosome 22q13-qter (refs 1,2). Because several other SCA subtypes show trinucleotide repeat expansions, we examined microsatellites in this region. We found an expansion of a pentanucleotide (ATTCT) repeat in intron 9 of SCA10 in all patients in five Mexican SCA10 families. There was an inverse correlation between the expansion size, up to 22.5 kb larger than the normal allele, and the age of onset (r2=0.34, P=0.018). Analysis of 562 chromosomes from unaffected individuals of various ethnic origins (including 242 chromosomes from Mexican persons) showed a range of 10 to 22 ATTCT repeats with no evidence of expansions. Our data indicate that the new SCA10 intronic ATTCT pentanucleotide repeat in SCA10 patients is unstable and represents the largest microsatellite expansion found so far in the human genome.

Neutrophil activation after burn injury: contributions of the classic complement pathway and of endotoxin.

We attempt to elucidate the mechanisms of neutrophil (PMN) activation after burn injury. We previously reported prolonged elevations of PMN cell surface complement (C) opsonin receptor levels after burn trauma with a corresponding period of depressed PMN chemotaxis to C5a, which suggests that the C product, C5a, was responsible for PMN activation. However, a lack of direct correlation of C activation with C receptor levels soon after injury raised the possibility of a second PMN-activating substance. We therefore investigated the effect of endotoxin (LPS) on the expression of the C receptors (CR1 and CR3) by normal human PMNs. Concentrations from 0 to 50 ng/ml of LPS 026:B6 caused a dose response increase in the PMN surface expression of CR1 and CR3 as assessed by monoclonal antibody binding and indirect immunofluorescence. The relative CR1-dependent fluorescence rose from a mean of 50 to 385 and CR3 from 50 to 300. Chelation by ethylenediaminetetra acetic acid (EDTA) did not influence this dose response, thus ruling out the possibility of C activation by LPS--an inference supported by the lack of complement activation observed with these concentrations of LPS in normal serum. A similar dose response was obtained in the absence of other cell types or serum, which implies a direct effect that mimicked that of C5a. To determine the mechanism of the later, prolonged C activation after burn injury, we next examined C activation products in 22 patients with burn injuries. Elevations of plasma C3a desArg were present and persisted for 50 days. Elevations were at maximum levels on days 9 through 13 postburn (mean +/- standard error of mean [SEM], 496 +/- 47 ng/ml versus normal 113 +/- 32; p less than 0.01). These were accompanied by elevations of C4a desArg (917 +/- 154 ng/ml versus normal 424 +/- 50; p less than 0.01), which are indicative of classic pathway activation. Finally, we examined PMN function, phagocytosis and percentage killing of Staphylococcus aureus, and found PMN function to be unaltered in the 22 patients. Thus PMN activation after burn injury appears to be caused by LPS soon after injury and by C5a later after injury and affects only selected PMN functions.

Role of ECMO in neonatal myocardial infarction.

A neonate with myocardial infarction who failed to respond to conventional treatment was supported by extracorporeal membrane oxygenation (ECMO). Severe mitral valve regurgitation necessitated mitral valve replacement while receiving ECMO following which the infant was successfully weaned. ECMO should be considered for potentially treatable causes of catastrophic heart failure.

Paediatricians' perception of the use of extracorporeal membrane oxygenation to treat meconium aspiration syndrome.

This questionnaire study was designed to determine how consultant paediatricians perceived the value of extracorporeal membrane oxygenation (ECMO) in the treatment of meconium aspiration syndrome (MAS). A significant number believed that the survival of infants with MAS who received ECMO was lower than reported. Early discussion with an ECMO centre will ensure appropriate timing of referral.

The changing incidence of neural tube defects in Scotland.

The impact of neural tube defects on neonatal surgery has been declining in Scotland over the past two decades. The Scottish statistics for neural tube defects were studied from 1971 to 1988. The incidence of neural tube defects in Scotland has declined from 5.50 to 1.10 per 1,000 births over this period (3.00 to 0.58 per 1,000 births for spina bifida and 2.50 to 0.52 per 1,000 births for anencephaly). Antenatal maternal alpha-fetoprotein (AFP) screening was introduced to Scotland on a wide scale in 1976. The number of terminations for anencephaly peaked in 1980 (85), and for spina bifida in 1981 (70), and both have since declined. The Scottish birth rate has been about 67,000 per year over this period. The declining incidence of neural tube defects is not explained by the effect of antenatal screening and terminations alone. A downward trend was apparent before 1976, and although antenatal screening has had a considerable impact on anencephaly births (peak terminations 89% in 1983), it has had only a modest impact on spina bifida births (peak terminations 53% in 1984). We conclude that the natural decline in incidence of neural tube defects is the major factor in the observed decline in neonatal surgical admissions for these defects.

Primary (retractile) mesenteritis in a child.

We report a case of primary retractile mesenteritis presenting as acute abdominal pain requiring surgery in a 3-year-old boy. At laparotomy, a hemoperitoneum was discovered and the diagnosis of primary mesenteritis was made with the aid of frozen section biopsy of the small bowel mesentery. No resection was necessary, and he made an uneventful recovery and remains well on follow-up.

Experience with bilateral renal artery stenosis as a cause of hypertension in childhood.

Since 1981, eight children have been treated at this hospital for hypertension due to bilateral renal artery stenosis (RAS). Useful diagnostic studies were DTPA renal scan following pretreatment with captopril, and selective renal angiography. All patients underwent attempted surgical revascularization of the RAS and three had aortoaortic bypass of an abdominal aortic narrowing. Of the 14 kidneys that had repair of RAS, a successful outcome was obtained in 11 (80%). Three patients required unilateral nephrectomy. Five of eight patients are normotensive and off all medications, and three are normotensive on reduced medication doses.

Fiberoptic localization of the upper pouch in esophageal atresia.

This report describes a technique that the authors developed as a simple, quick means of identifying the proximal pouch in neonates with esophageal atresia by fiberoptic instrumentation.

Gastroschisis in the decade of prenatal diagnosis: 1983-1993.

Fifty cases (24 males, 26 female) of gastroschisis were admitted to the Regional Neonatal Surgical Unit at the Royal Hospital for Sick Children in Yorkhill, Glasgow, between January 1983 and October 1993. The mean birthweight was 2.17 kgs and mean gestation was 35.8 weeks. Prenatal diagnosis was made by ultrasound scan in 39 cases (78%) and 33 (66%) were delivered in the Regional Obstetric Unit and Fetal Medicine Centre at the Queen Mother's Hospital, Yorkhill, Glasgow, immediately adjacent to the neonatal surgical unit. Spontaneous vaginal delivery occurred in 23 (46%) but Caesarean section was performed in 27 (54%). Sixteen Caesarean sections were emergencies and 11 elective (5 on account of dilated bowel loops). Associated bowel problems were noted in 11 (22%)--atresia (5), stenosis (2), ischaemia (1), duodenal perforation (1), ileal perforation (1) and jejunal band obstruction (1). Primary closure was achieved in 42 (84%) and there were 5 deaths (10%). Prenatal diagnosis and mode of delivery showed no direct correlation with mortality (10%) in this series. Emergency Caesarean section was necessary for fetal indications in 28%. The prediction of compromised or damaged intestine by prenatal ultrasound was unreliable and the majority of cases of atresia and stenosis escaped detection. However, it is concluded that prenatal diagnosis and delivery in a regional centre offers the best outcome for the fetus. Further study is needed to define "at risk" pregnancies and fetuses and to determine the role of intervention.

Post-mortem findings in fetal and neonatal congenital diaphragmatic hernia.

Analyses of survival data of neonates born with congenital diaphragmatic hernia (CDH) can be misleading. There is a hidden mortality only apparent when fetuses with CDH are included in the analysis. A retrospective review of all post mortems with a diagnosis of CDH in the West of Scotland over a 10-year period was carried out. Congenital anomalies were identified and heart and lung weights were compared with controls (infants dying of non-cardiorespiratory causes). 70 Pm reports were studied. Major congenital anomalies were present in 53% (18/ 47 live born, 19/23 not live born). Neural tube defects, cardiac and chromosomal anomalies were the most common. Antenatal detection rate was 17% in live-born infants. In infants dying within the first week of life lung weights showed severe pulmonary hypoplasia, but heart weights were within the normal range. Detailed antenatal scanning needs to be considered if the detection rate for CDH is to improve in this region.

Academic preparation of athletic trainers as counselors.

Athletic trainers have assumed several roles and responsibilities over the years, but perhaps there is no more important role than that of a counselor. Are they prepared to do so? One hundred and thirty-two modified Revised Wylie Inventories were mailed to college/university athletic trainers to examine their educational preparation and experiences with counseling in various areas. Most athletic trainers surveyed reported that they were predominantly counseling in the areas of injury prevention, injury rehabilitation, and nutrition, and felt academically prepared to do so. However, it was reported that preparation to counsel in other less common areas (eg, family matters, financial matters, etc) was not adequately addressed in academic programs. The athletic trainers surveyed sought continuing education in order to meet the other counseling needs of student-athletes. Although they used several psychological referral services, it was apparent that most athletic trainers frequently served as counselors on many nonorthopedic topics. We suggest that athletic training educators consider incorporating both academic knowledge and clinical experience in a wider variety of counseling areas into their curricula.

The hidden mortality of congenital diaphragmatic hernia: a 20-year review.

AIMS: The true mortality associated with congenital diaphragmatic hernia (CDH) is hidden because survival analyses do not include fetuses with CDH. A retrospective review of all postmortems (PMs) with a diagnosis of CDH over a 20-year period was carried out to highlight this hidden mortality and also measure the nature and number of associated anomalies. METHODS: Postmortem case record details were reviewed for the period January 1986 to December 2005. Data were collected on live birth, stillbirth, therapeutic abortion, and spontaneous abortion. RESULTS: There was a decline in the annual number of PMs during the period of the study. The median for the four 5-year intervals being 609 (570-657), 528 (488-565), 515 (413-537), and 373 (357-388). A total of 130 PMs were identified, which included a diagnosis of CDH; 97 (75%) were left sided, 22 (17%) were right sided, and 11 (8%) were bilateral. There were 69 live births, 46 therapeutic abortions, 10 stillbirths, and 5 intrauterine deaths; 22% were right sided/bilateral in the live and therapeutic abortion groups, whereas 53% were right sided/bilateral in the latter 2 groups. Of 130, 82 (63%) had major associated anomalies, and 50% of these had at least 1 further major anomaly. The commonest categories of anomalies were cardiac (30), gastrointestinal/abdominal wall defect (28), and neural tube defects (25). CONCLUSIONS: The true incidence of CDH is considerably higher than that seen in neonatal surgical practice. The decline in number of PMs in our region will exacerbate the underestimation of the true incidence. There is a higher incidence of right-sided/bilateral hernias and more than one major anomaly in those who die in utero.

Monocyte activation after burns and endotoxemia.

We describe the settings in which monocytes (M) are activated, as monokines may mediate organ dysfunction occurring after surgery and sepsis. To monitor M activation, we measured the relative number of M cell surface receptors for C3b and iC3b by indirect immunofluorescence. M exposed to increasing concentrations of endotoxic lipopolysaccharide (LPS) expressed increased mean cell surface C3b receptor-dependent fluorescence (35 buffer alone vs 354 LPS at 1000 ng/ml) and iC3b receptor-dependent fluorescence (78 vs 404). To determine whether this M activation could be reproduced by endotoxemia, normal volunteers were randomly administered saline or a single dose of LPS (20 u/kg). We found increased M cell surface C3b receptors 4 hr after LPS (341 LPS (n = 22) vs 168 saline (n = 20)) which returned to control levels at 24 hr. A similar transient increase was seen at 4 hr with M cell surface iC3b receptors (304 LPS (n = 23) vs 104 saline (n = 20)). To determine whether this could be used clinically, seven patients with burns (10-70% body surface area) were serially sampled up to 50 days. Each patient demonstrated elevations of M cell surface C3b and iC3b receptors, which gradually decreased over many weeks. For the group as whole, mean M cell surface C3b receptor-dependent fluorescence was 287, Days 0-5 postburn (vs 132 in 147 normals); 315, Days 6-9; 217, Days 10-13; 237, Days 14-19; and 185, Days 20+.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of computed tomography and ultrasonographic imaging in the assessment of blunt abdominal trauma in children.

BACKGROUND: Computed tomography (CT) has become established in the assessment of paediatric blunt abdominal trauma. However, advances in diagnostic imaging necessitate reassessment of the role of available diagnostic modalities. METHODS: Experience at a paediatric teaching hospital over a 5-year period was reviewed, with direct comparison of CT against ultrasonographic imaging in 26 children presenting with acute blunt abdominal trauma. RESULTS: Intra-abdominal injury was diagnosed by CT in 23 of 24 patients compared with 21 on ultrasonography, although ultrasonography identified organ-specific injury in only 12 of 24 patients. CT was superior in the assessment of the multiply injured child, and identified spinal and pelvic injuries in three patients. CT augmented plain chest radiography in ten patients with associated thoracic injuries. CONCLUSION: CT is the imaging modality of choice in children with severe abdominal trauma but ultrasonography is a reasonable technique to arouse diagnostic suspicion in less severe injuries or where CT is unavailable or delayed.

Neonatal tumours: Glasgow 1955-86.

Fifty one neonatal tumours were diagnosed in Glasgow over a 32 year period. The most common tumours were teratomas (n=19), others being renal tumours (n=9), soft tissue sarcomas (n=8), neuroblastomas (n=7), and others (n=8). Of the total, 31% were malignant. Neonatal tumours pose difficult problems of management, and because of their comparative rarity and the great potential for cure we recommend that all centres dealing with such patients should contribute to and benefit from a Neonatal Tumour Registry.

An epidemic of trichinosis after ingestion of wild pig in Hawaii.

Forty-five percent of young adults who ate roast wild pig at a barbecue in Hawaii experienced an illness compatible with trichinosis. Eosinophilia was present in all of those who were ill and in none who remained well. There were no positive results in skin tests with commercial skin-test antigen. Latex agglutination and counterelectrophoresis were equally good methods for the diagnosis of trichinosis and were more sensitive than the bentonite flocculation test. Levels of IgE in those with illness and eosinophilia were not significantly different from the levels in persons who remained well. It is concluded that skin tests should be abandoned until an improved antigen becomes available, that the relative value of diagnostic serologic methods require continued evaluation, and that levels of IgE may not rise significantly after trichinosis.