Heparin and in-vitro experimental lung hypoplasia

 Pulmonary hypoplasia (PH) is a leading contributor to the lethality of congenital diaphragmatic hernia (CDH). Studies now suggest that PH arises prior to visceral herniation. Growth factors (GF) are pivotal to this embryonic lung growth. With striking in-vitro effects on lung morphogenesis, GF are under investigation as therapies for PH. Heparin modulates the kinetics of heparan-sulphate binding ligands that drive lung development. We hypothesised that heparin may rescue PH by favourable alteration of endogenous pulmonary GF activity. Normal and hypoplastic lung primordia were microdissected on day 13.5 of gestation and cultured for up to 78 h in plain media with and without heparin. In-vitro morphological development was studied by serial measurements of terminal bud count, lung area, and lung perimeter. Nitrofen-exposed lungs cultured with heparin showed no significant improvements in terminal bud count, lung area, and lung perimeter at 30, 54, and 78 h compared to untreated hypoplastic lungs maintained in vitro. In normal lungs heparin demonstrated no sustained significant morphological effects compared to untreated control lungs. In this study, heparin did not stimulate branching morphogenesis of normal or hypoplastic lungs in our organ culture system. Known at higher concentrations to inhibit smooth-muscle proliferation, heparin may ameliorate pulmonary vascular hypermuscularisation with the prospect of benefiting CDH infants on extracorporeal membrane oxygenation. Future studies will address the impact of exogenous GF on hypoplastic lung development in organ culture.     

Athetoid quadriplegia and literacy

OBJECTIVE: To compare literacy levels in athetoid quadriplegic (AQ) patients born in the 1960s and 1970s with those born in the 1980s and 1990s. METHODOLOGY: Nine patients with AQ born between 1966 and 1972 were compared with eight patients born between 1983 and 1991. RESULTS: Reading difficulties were found in almost all patients with AQ, despite normal intellect. Those in the earlier period were for the most part functionally literate, while those in the later period were functionally illiterate. CONCLUSIONS: Specific and intensive reading education may be required in patients with AQ to obtain functional literacy.     

Intrapulmonary shunting in the biliary atresia/polysplenia syndrome: reversal after liver transplantation

One hundred and seventy three children, including 93 with biliary atresia, received liver grafts at Addenbrooke's Hospital between 1983 and 1993. Of these, only seven developed cyanosis due to intrapulmonary shunting as a complication of their liver disease, and all seven of these had the biliary atresia/polysplenia syndrome. Intrapulmonary shunting was confirmed by a radioisotope scan in four children. Only one child with the syndrome did not have cyanosis when undergoing transplantation. Seven of the eight children are alive 6-54 months after transplantation, with normal pulmonary and hepatic function. Cyanosis recurred in one child who developed chronic rejection with liver failure. In conclusion: (a) there is a strong association between the biliary atresia/polysplenia syndrome and cyanosis due to intrapulmonary shunting; (b) intrapulmonary shunting is fully reversible after successful liver transplantation; and (c) cyanosis, once present, is progressive, and these children should be considered for liver transplantation as soon as it occurs.     

Neurological crisis in hereditary tyrosinaemia and complete reversal after liver transplantation

A 19 month old Indian girl with tyrosinaemia developed a severe generalised neuropathy involving both phrenic nerves. Treatment with haemarginate failed to improve her condition. After liver transplantation the raised concentrations of the neurotoxin delta amino-laevulinic acid returned to normal and gradual but complete neurological recovery occurred over a period of 13 months.     

Use of partition models to evaluate guidelines for mixtures of volatile organic compounds

Partition models based on the octanol-air parition coefficients and associated quantitative structure-activity relationships (QSARs) have been developed to describe the triggering of odor response and nasal irritation by common volatile organic compounds (VOCs). This study made use of the QSARs developed by Hau and Connell (1998, Indoor Air 8, 23-33) and Hau et al. (1999, Toxicol. Sci. 47, 93-98) to evaluate risk-based guidelines on the airborne concentrations of common VOCs in the nonindustrial environment. A new concept referred to as the "apparent internal threshold concentration" was developed for evaluating the odor and nasal pungency responses to a typical low-concentration VOC mixture described by Otto et al. (1990, Neurotoxicol. Teratol. 12, 649-652). The assessment indicated that odor can be detected at a total VOC concentration of about 3 mg/m(3), consistent with the findings of Molhave et al. (1991, Atmos. Environ. 25, 1283-1293). Nasal pungency, according to our assessment, should not ocur at a total concentration of 25 mg/m(3), which is apparently in conflict with the findings of Molhave (1986, ASHRAE Trans. 92(1A), 306-316). It can be inferred from this investigation that pure nasal pungency without the influence of odor is unlikely to result from exposure to low-concentration VOC mixtures typically found in the nonindustrial environment.     

Effect of pretreatment with carbimazole on early outcome following radio-iodine (131I) therapy

Of a group of 55 thyrotoxic patients given therapeutic radio-iodine (¹³¹I), 24 were made euthyroid with carbimazole before¹³¹I: the remainder were given¹³¹I alone. Carbimazole was discontinued 5 days before¹³¹I was administered. By 3 months after¹³¹I treatment there was a greater incidence of hypothyroidism in the group given¹³¹I alone (42% vs 25%), but a lower incidence of persistent thyrotoxicosis (16% vs 46%), (P>0.05). One year after treatment a similar proportion of each group had persistent thyrotoxicosis (21% vs 23%), but there remained a lower incidence of hypothyroidism in the group pretreated with carbimazole (25% vs 45%). It is suggested that pretreatment with carbimazole reduces the degree of radiation induced thyroid damage.