Management of the neonate at the limits of viability: the Dutch viewpoint

Due to ever-improving medical technology over the course of the last century, the limit of viability has been lowered from around 32 weeks of gestation, first to 28 weeks and, in recent decades, to as low as less than 24 weeks. Long-term follow-up studies (Project on Preterm and Small-for-Gestational-Age Infants, Leiden Follow-up Project on Prematurity, Epidemiological Project for ICU Research and Evaluation, Étude Epidémiologique sur les Petits Ages Gestationnels, Extremely Preterm Infants in Belgium), however, have shown high percentages of deaths and/or disabilities at lower gestational ages in surviving children. Many parents and children are burdened with lifelong iatrogenic disabilities. As a result, the Dutch Paediatric Association and the Dutch Society of Obstetrics and Gynaecology have laid down joint rules for the management of expected/threatened preterm delivery.     

Carcinogenic polycyclic aromatic hydrocarbons increase intracellular Ca2+ and cell proliferation in primary human mammary epithelial cells

Previous studies have shown that polycyclic aromatic hydrocarbons (PAHs) mobilize intracellular Ca2+ in human T cells by inositol trisphosphate-dependent mechanisms resulting from activation of phospholipase C-gamma by SRC-related protein tyrosine kinases, thereby mimicking antigen-receptor activation. Ca2+ appears to play an important second messenger role in growth factor control of cell proliferation in human mammary epithelial cells (HMEC), such as the epidermal growth factor receptor pathway. The purpose of the present studies was to determine if PAHs are able to increase intracellular Ca2+ in primary cultures of HMEC and increase cell proliferation. Two carcinogenic and two non-carcinogenic PAHs were tested for their ability to increase intracellular Ca2+ in HMEC. The carcinogenic PAHs dimethylbenz[a]anthracene (DMBA) and benzo[a] pyrene (BaP) were able to cause Ca2+ elevation in HMEC at early time points (2 h) and caused sustained alterations in Ca2+ homeostasis (18 h). DMBA showed maximal effects at early time points (2 h), while BaP showed maximal effects on sustained Ca2+ (18 h). 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a potent dioxin and tumor promoter, produced maximal Ca2+ elevation at 2 h, with a return to near baseline levels by 6 h. The non-carcinogenic PAHs benzo[e]pyrene and anthracene did not significantly alter intracellular Ca2+ at any time point. alpha-Naphthoflavone significantly reduced the Ca2+ response induced by BaP treatment, but not by DMBA or TCDD, suggesting that P450 1A or 1B metabolism of BaP may be important in the sustained Ca2+ elevating response. In evaluating the effects of BaP on HMEC proliferation, BaP was found to increase the number of cells recovered after 4 days in culture in the absence or presence of various concentrations of epidermal growth factor. These studies provide initial evidence that Ca2+ signaling may be associated with mitogenesis in HMEC, which may play a role in tumor promotion and progression produced by PAHs.      

Urinary tract infection: a comparison of four methods of investigation

The optimal regimen for investigating children with urinary tract infection (UTI) remains uncertain. Ultrasonography, contrast micturating cystourethrography (MCU), intravenous urography (IVU), and technetium-99m dimercaptosuccinic acid (DMSA) studies were performed in 58 children with UTI under 14 years of age attending two teaching hospitals and the results compared. All four investigations were normal in 12 children. In 36 with vesicoureteric reflux (VUR) on MCU, dilatation was reported on ultrasonography in eight children. Radiological renal scarring was seen in 20 children; it was suspected on ultrasonography in nine, with dilatation alone in four, and a normal report in seven. Duplex kidneys identified on IVU were unrecognised on ultrasonography or DMSA studies; ultrasonography showed no change corresponding to presumed acute defects on DMSA studies that later resolved. Disparities were observed at all ages. This study suggests that ultrasonography is unreliable in detecting VUR, renal scarring, or inflammatory change and, alone, is inadequate for investigating UTI in children.     

Liver transplantation for homozygous familial hypercholesterolaemia

Homozygous familial hypercholesterolaemia is a rare inherited condition with an incidence of approximately one in a million. It is associated with severe premature atherosclerosis and early death from cardiovascular complications. The results of liver transplantation reported to date have suggested only partially effective reduction of the hypercholesterolaemia. Three boys with familial hypercholesterolaemia, aged 10.0 to 15.1 years, received liver grafts at Addenbrooke's Hospital. Their untreated fasting lipid concentrations were grossly raised. All three had angiographic evidence of coronary atheroma and two had exertional angina. One child had such severe atheroma that coronary artery bypass surgery was considered necessary before liver transplantation. All three had straightforward operative and postoperative courses and their lipid concentrations returned rapidly to normal. One boy developed chronic rejection requiring retransplantation. Currently all three boys are well, on normal diets, and with normal liver function. It is concluded that (1) liver transplantation offers highly effective treatment for this lethal condition, (2) timing the operation is difficult but it should be undertaken before coronary artery disease has progressed too far (when combined liver and heart transplantation may be the only possibility), and (3) in well grown children with no previous abdominal surgery the immediate risks of liver transplantation are low but chronic rejection remains a danger.     

The spleen in Hodgkin disease: diagnostic value of CT

Findings of CT of the spleen were compared with those of histologic examination in 35 patients who had Hodgkin disease. CT provides a simple way to calculate splenic size. This index is also of value in the assessment of the histologic state of the spleen. An accuracy rate of 91%, specificity of 94%, and a sensitivity of 89% in diagnosing splenic localization of lymphoma was found in this study.