Comparative assessment of enzyme-linked immunosorbent assay and Western blot for the diagnosis of toxocariasis in patients with skin disorders

Background  The link between various chronic skin disorders and toxocariasis was previously demonstrated by case reports and several case–control studies. However, these previous studies were based only on the Toxocara canis excretory-secretory–enzyme-linked immunosorbent assay (TES–ELISA) serological technique, which is not specific due to cross-reactivity with parasites of the genera Anisakis or Ascaris . Immunoblot analysis is highly specific and can detect very low levels of Toxocara antibodies. Therefore, this technique may be useful in the identification of Toxocara infection in patients with chronic skin disorders.
Objectives  Because urticaria and pruritus/prurigo are skin conditions previously associated with toxocariasis, we carried out a prospective study using both TES–ELISA and Toxocara Western blot on 113 patients with either chronic urticaria ( n  =   84) or chronic pruritus ( n  =   29).
Methods  Patients were matched with controls according to gender, age and residence location (rural or urban area). Data were analysed using a Mantel–Haenszel χ² test.
Results  The proportion of positive TES–ELISA results was not significantly different for patients with chronic skin disorders (urticaria or pruritus/prurigo) from that of control subjects. However, the proportion of positive immunoblot results was significantly higher for patients with chronic urticaria than for control subjects ( P  =   0·009).
Conclusions  Our study demonstrates the need to perform Western blotting immunodiagnosis, whatever the TES–ELISA result, to improve diagnosis of human toxocariasis in patients with chronic urticaria caused by Toxocara infection.     

Positive association of up-regulated Cripto-1 and down-regulated E-cadherin with tumour progression and poor prognosis in gastric cancer

Aims:  Cripto-1 may be capable of up-regulating signalling molecules associated with epithelial-to-mesenchymal transition (EMT), an important event characterized by loss of E-cadherin during malignant tumour progression and metastasis. The aim was to investigate the expression of Cripto-1 and E-cadherin in relation to clinicopathological features and patient prognosis of gastric cancer.
Methods and results:  The expression of Cripto-1 and E-cadherin was studied by immunohistochemistry in 118 gastric cancer cases. Up-regulated Cripto-1 (CR+) was found in 54% (64/118) of cases, whereas down-regulated E-cadherin (E-cad−) was found in 70% (83/118) of cases. Either CR+ or E-cad− was associated with lymph node metastasis, liver metastasis and late TNM stage ( P  < 0.05). Patients with either CR− or E-cad+ showed higher 5-year survival rates than those with CR+ or E-cad− ( P  = 0.0012 and P  = 0.0017, respectively). When combined, evaluation of these two proteins, simultaneous CR+ and E-cad− (CR+/E-cad−) in cancer was strongly associated with the above three aggressive clinicopathological features ( P  < 0.001) and indicated the worst patient survival ( P = 0.0001). Multivariate analysis revealed that CR+/E-cad− was an independent prognostic factor in gastric cancer.
Conclusions:  Combined analysis of Cripto-1 and E-cadherin has significant value in evaluating the metastatic potential of gastric cancer and predicting patient prognosis.     

Functional consequences of a SDHB gene mutation in an apparently sporadic pheochromocytoma

Three genes encoding for mitochondrial complex II proteins are linked to hereditary paraganglioma. We have recently shown that an inactivation of the SDHD gene is associated with a complete loss of mitochondrial complex II activity and a stimulation of the angiogenic pathway (Gimenez-Roqueplo, A. P., J. Favier, P. Rustin, J. J. Mourad, P. F. Plouin, P. Corvol, A. R?tig, and X. Jeunemaitre, 2001, Am J Hum Genet 69:1186-1197). Here, we relate the case of a malignant sporadic pheochromocytoma induced by a germline missense mutation of the SDHB gene. Within the tumor, a loss of heterozygosity at chromosome 1pter led to a null SDHB allele and to a complete loss of complex II enzymatic activity. In situ hybridization and immunohistochemistry experiments showed a high expression of hypoxic-angiogenic responsive genes, similar to that previously observed in inherited-SDHD tumors. This observation highlights the role of the complex II mitochondrial genes in the oxygen-sensing pathway and in the regulation of angiogenesis of neural crest-derived tumors.     

Neonatal outcome after exposure to beta adrenergic blockers late in pregnancy]

OBJECTIVES: To analyse neonatal effects after in utero betablockers exposure and the pertinence of recommendations delivered by our team. POPULATION AND METHODS: We report 44 pregnancies exposed to betablockers during the late pregnancy including the period of delivery about which the Regional Pharmacovigilance Center of Tours (CRPV) was questionned. RESULTS: Among the 39 children for whom we know the follow up, 22 had neonatal adverse effects of which 19 could be explained by in utero exposure to betablockers i.e. an hypoglycaemia (11 times), a bradycardia (six times), a bradycardia and hypoglycemia (one time) and an hypotension (one time). A drug-related effect was retained for eleven newborns (27%) and another etiology could be evoked in the eight others. The risk of neonatal adverse effects seems to increase in newborns exposed to labetalol (5/11), to betaxolol (1/2) or to propranolol (2/6) or when the dose is high. The eight newborns who had intrauterine growth retardation were generally more often exposed to atenolol than eutrophic newborns. Four babies had malformations. CONCLUSIONS: Our recommendation was an hospitalization 44 times (100%) to monitor heart rate, blood pressure and glycemia. When the follow-up is known, hospitalization was performed in 88% of the cases. Glycemia, heart rate and blood pressure were monitored in all the hospitalized children and in three of the five not hospitalized children. Our recommendation seems particularly justified with regard to hypoglycemia which is often asymptomatic but whose consequences can be severe. Atenolol often provider of intrauterine growth retardation and labetalol more often at the origin of neonatal adverse effects are probably to avoid during pregnancy.     

Spectrum of hemojuvelin gene mutations in 1q-linked juvenile hemochromatosis

Juvenile or type 2 hemochromatosis (JH) is transmitted as a recessive trait that leads to severe iron overload and organ damage typically before age 30 years. Linkage to a locus on chromosome 1q has been found in most patients with JH. The recently identified causal gene encodes hemojuvelin, a protein with a proposed crucial role in iron metabolism. A second, rare type of JH, with clinical expression identical to the 1q-linked form, is due to inactivation of hepcidin, the key regulator of iron homeostasis. Here we report the spectrum of mutations of the hemojuvelin gene (HJV) in 34 patients who did not show hepcidin mutations. This represents the largest cohort of patients with JH collected worldwide. We identified 17 different (16 novel) mutations of HJV, both at the homozygous and at the compound heterozygous state. Mutations either generate premature termination codons or were missense substitutions, affecting highly conserved residues, relevant to the protein structure and/or function.     

Loss of visual acuity due to choroidal ischemia in Fabry's disease

We report a case of a 21-year-old man with Fabry's disease who presented with a sudden decrease in visual acuity to 20/200 in the left eye. Pale areas with a lobular choroidal distribution were seen on fundus examination. No retinal vascular causes were found on further evaluation. With anticoagulation treatment, the patient's subsequent course was good, with visual recovery to 20/25 and normalization of the funduscopic appearance. Recovery of both visual acuity and the pale, lobular areas suggested a choroidal etiology, probably ischemic because of the sudden onset. Choroidian ischemia is therefore a cause of visual acuity loss in Fabry's disease, so far not described in the literature.     

Second malignancy risk associated with treatment of Hodgkin's lymphoma: meta-analysis of the randomised trials.

BACKGROUND: Despite several investigations, second malignancy risks (SMR) following radiotherapy alone (RT), chemotherapy alone (CT) and combined chemoradiotherapy (CRT) for Hodgkin's lymphoma (HL) remain controversial. PATIENTS AND METHODS: We sought individual patient data from randomised trials comparing RT versus CRT, CT versus CRT, RT versus CT or involved-field (IF) versus extended-field (EF) RT for untreated HL. Overall SMR (including effects of salvage treatment) were compared using Peto's method. RESULTS: Data for between 53% and 69% of patients were obtained for the four comparisons. (i) RT versus CRT (15 trials, 3343 patients): SMR were lower with CRT than with RT as initial treatment (odds ratio (OR) = 0.78, 95% confidence interval (CI) = 0.62-0.98 and P = 0.03). (ii) CT versus CRT (16 trials, 2861 patients): SMR were marginally higher with CRT than with CT as initial treatment (OR = 1.38, CI 1.00-1.89 and P = 0.05). (iii) IF-RT versus EF-RT (19 trials, 3221 patients): no significant difference in SMR (P = 0.28) although more breast cancers occurred with EF-RT (P = 0.04 and OR = 3.25). CONCLUSIONS: Administration of CT in addition to RT as initial therapy for HL decreases overall SMR by reducing relapse and need for salvage therapy. Administration of RT additional to CT marginally increases overall SMR in advanced stages. Breast cancer risk (but not SMR in general) was substantially higher after EF-RT. Caution is needed in applying these findings to current therapies.     

Percutaneous central iv access in the neonate: experience with 535 silastic catheters

We examined 535 central venous catheterizations performed in a neonatal intensive care unit. A total of 273 catheters were positioned using intra-atrial ECG monitoring. With an average indwelling time of 23 days, we noted one complication for every 153 indwelling catheter days. A diagnosis of sepsis was confirmed on 22 occasions (4.1 %). Sepsis occurred more often in infants with a birth weight < 1000 g (6.9%) compared with infants 1000g (3.1%). The risk of phlebitis was highest when the saphenous vein was used as the puncture site. The lowest risk of phlebitis was when the basilic vein was chosen. Five cases of thrombosis, two of myocardial perforation and one intravascular catheter breakage were registered. Catheter placement under ECG monitoring proved to be a very suitable method for reducing the incidence of malpositioning. There were no side effects specific to the ECG method. The ECG method can be used safely and makes radiological control usually unnecessary. Central venous catheters, newborn infant, parenteral nutrition, silicone catheters