DNA testing for fragile X syndrome in schools for learning difficulties

Fragile X syndrome is the most common inherited cause of mental retardation. Early diagnosis is important not only for appropriate management of individuals but also to identify carriers who are unaware of their high risk of having an affected child. The disorder is associated with a cytogenetically visible fragile site (FRAXA) at Xq27.3, caused by amplification of a (CGG)n repeat sequence within the gene at this locus designated FMR1. Clinical and molecular studies have been undertaken to screen for fragile X syndrome in 154 children with moderate and severe learning difficulties of previously unknown origin. Southern blot analysis of peripheral blood showed the characteristic abnormally large (CGG)n repeat sequence associated with fragile X syndrome in four of the 154 children. The findings were confirmed by cytogenetic observation of the fragile site and by further molecular studies. The families of the affected children were offered genetic counselling and DNA tests to determine their carrier status. These findings show that there are still unrecognised cases of fragile X syndrome. Given the difficulty of making a clinical diagnosis and the implications for families when the diagnosis is missed, screening in high risk populations may be justified. The issues involved in screening all children in special schools for fragile X syndrome are discussed.     

Growth, puberty and obesity after treatment for leukaemia

Final height, body proportions, pubertal growth and body mass index were studied retrospectively in 142 survivors of acute lymphoblastic leukaemia (ALL). Treatment consisted of combination chemotherapy and cranial irradiation (18 or 24 Gy). Significant standing height loss and disproportion, with a relatively short back, was seen in both radiation dose groups. Girls were more severely affected than boys. Pubertal growth was adversely affected, with a reduction in peak height velocity in both sexes. Puberty occurred early in girls but at the normal time in boys. Nearly half the group were obese at final height, with no significant difference in incidence between the sexes. The relative roles of cranial irradiation and chemotherapy in the disturbance of growth, puberty and body composition observed in survivors of childhood ALL remain unclear. The aetiology is almost certainly multifactorial, with radiation-induced growth hormone insufficiency, early puberty, steroids and chemotherapy all having a role.     

Renal transplantation and osteoporosis

A cross sectional study assessed the bone mineral density (BMD) of 20 young adult patients who received a renal transplantation in childhood. The BMD of the lumbar spine, mainly trabecular bone, and of the total body, mainly cortical bone, were measured and expressed as an SD score. Fourteen patients (70%) had a BMD SD score of the lumbar spine below -1, of whom six patients were below -2. Fifteen patients (75%) had a BMD SD score of the total body below -1, of whom seven patients were below -2, Both trabecular and cortical bone appeared to be involved in the osteopenic process. The cumulative dose of prednisone was inversely correlated to both lumbar spine and total body BMD SD score. In a multiple regression analysis the cumulative dose of prednisone appeared to be the only factor with a significant effect on BMD SD score. Most young adult patients who had received a renal transplantation in childhood had moderate to severe osteopenia. Corticosteroid treatment played a major part in the development of osteopenia in these patients.     

Ultrasound screening of families with abdominal aortic aneurysm

Recent observations suggest that first degree relatives of patients with an abdominal aortic aneurysm (AAA) are also at risk for the development of this disorder. The first degree relatives of 130 adults with known AAA were invited to attend for an ultrasound examination. Fifty-two eligible relatives (mean age 53 years, range 41–73) from 38 families underwent sonographic screening. Using standard ultrasound criteria no participants were identified with an asymptomatic AAA. Thus, ultrasound of families of patients with AAA has a low yield and may not be useful for screening purposes.     

Increased cerebral blood flow after brain arteriovenous malformation resection is substantially independent of changes in cardiac output

Brain arteriovenous malformation (BAVM) resection can result in an acute increase in cerebral blood flow (CBF) of unclear etiology. This observational study investigated the relationship between changes in CBF and cardiac output (CO) in patients undergoing microsurgical resection of BAVMs. In 20 patients undergoing a BAVM resection during an isoflurane-based anesthesia, we measured CBF and systemic cardiovascular parameters immediately before and after BAVM resection. CBF was measured on the hemisphere ipsilateral to the lesions and on the contralateral side, using intravenous cold 133Xe washout. Cardiac output was measured using thermodilution technique via a pulmonary artery catheter. There was an increase in global CBF after resection (25 +/- 8 versus 31 +/- 13 mL/100 g/min, preresection versus postresection, mean +/- SD, P =.002), ipsilateral CBF (25 +/- 8 versus 31 +/- 13 mL/100 g/min, P =.002), and contralateral CBF (24 +/- 7 versus 30 +/- 13 mL/100 g/min, P =.003). There was no change in CO, mean systemic arterial pressure, central venous pressure, or pulmonary artery diastolic pressure. The change in CBFGLOBAL was not correlated with changes in CO (r =.154, P =.517). BAVM resection resulted in global increases in CBF that was not substantially related to changes in CO or other systemic parameters.     

Ethyl (3S,4aR,6S,8aR)-6-(4-ethoxycar- bonylimidazol-1-ylmethyl)decahydroiso-quinoline-3-carboxylic ester: a prodrug of a GluR5 kainate receptor antagonist active in two animal models of acute migraine

Amino diacid 3, a highly selective competitive GluR5 kainate receptor antagonist, exhibited high GluR5 receptor affinity and selectivity over other glutamate receptors. Its diethyl ester prodrug 4 was orally active in two models of migraine: the neurogenic dural plasma protein extravasation model and the nucleus caudalis c-fos expression model. These data suggest that a GluR5 kainate receptor antagonist might be an efficacious antimigraine therapy with a novel mechanism of action.     

Early complications after one hundred and forty-four consecutive hip revisions with impacted morselized allograft bone and cement

BACKGROUND: The use of impacted morselized allograft bone and cement in hip revision arthroplasty has been popular, but studies that specifically address intraoperative and postoperative complications have been scarce. METHODS: All complications that occurred during, and within the first year after, 144 consecutive hip revision arthroplasties (108 stems and 130 sockets) performed with impacted morselized allograft bone and cement were recorded. Clinical and radiographic follow-up evaluation was performed at three months and at one year after surgery for all patients except eight (seven who had died of causes unrelated to the hip surgery and one who had sustained a stroke). Of these eight patients, seven had a six-week and/or three-month follow-up evaluation. RESULTS: Thirty-nine femoral fractures occurred in thirty-seven hips; twenty-nine of the fractures occurred during surgery and ten, within five months after surgery. Of the intraoperative femoral fractures, twelve were proximal, nine were diaphyseal, and eight involved the greater trochanter. Of the postoperative femoral fractures, one was proximal and nine were diaphyseal. Other intraoperative complications were the creation of a femoral cortical window in seven hips and incidental perforation of the femoral cortex in fourteen. Multivariate analysis showed the risk factors for femoral fracture during or after revision to be concomitant disease, greater deficiency of the femoral bone stock, and an intraoperative femoral window or perforation. Other complications included dislocation of the femoral head in nine hips, deep infection in one hip, persistence of preoperative deep infection in one hip, and superficial wound infection requiring wound débridement in two hips. CONCLUSIONS: We found the complication rate to be high after hip revision arthroplasty performed with impacted morselized allograft bone and cement. The most serious complication was postoperative diaphyseal femoral fracture.