[Diagnostic image (362). A neonate with sternal malformation]. / Diagnose in beeld (362). Een zuigeling met een plekje op het sternum.

A newborn girl with sternal malformation developed large facial hemangiomas consistent with the PHACES association.

[Persistent neonatal hypoglycaemia caused by arterial positioning of the umbilical venous catheter]. / Persisterende onverklaarde neonatale hypoglykemie door arteriële positie van een navelvenelijn.

Two neonates, a girl born at 40 2/7 weeks weighing 4165 g and a boy born at 37 6/7 weeks weighing 4040 g, received umbilical venous catheters to help manage hypoglycaemia. The catheter was ineffective or only effective when high doses of glucose were used, due to what later appeared to be arterial positioning of the catheter. Both patients recovered without consequences. Persistent hypoglycaemia is a common problem in newborns and can cause severe neurological sequelae. A relatively uncommon cause is malpositioning of the umbilical catheter. Positioning in an artery leads to direct infusion of glucose into the pancreas, which causes hyperinsulinaemia and can lead to potentially dangerous nonketotic hypoglycaemia. Arterial positioning of the umbilical catheter should be ruled out at an early stage. Correct catheter positioning can be determined using careful inspection of the umbilical veins, radiological examination of the catheter position, blood gas analysis or vascular pulsation.

[Diagnostic images (169). A toddler not feeling well and having a rash. Eczema herpeticum]. / Diagnose in beeld (169). Een peuter met algehele malaise en huiduitslag. Eczema herpeticum.

A 1-year-old boy with eczema presented with fever and a rash, which was diagnosed as eczema herpeticum.

Schistosomiasis japonica in the Philippines: the long-term impact of population-based chemotherapy on infection, transmission, and morbidity.

The long-term impact of annual case-finding and chemotherapy with praziquantel on schistosomiasis japonica was examined in an 8-year longitudinal study in the Philippines. The prevalence, incidence, and intensity of infection and schistosome-induced hepatomegaly significantly decreased within 3-4 years of treatment and then stabilized despite continual population-based chemotherapy. Hepatomegaly rapidly developed in acutely infected persons, with 82% of subjects developing hepatic enlargement within 2 years of reinfection. These data suggest that abrupt discontinuation of current control measures in the Philippines may result in a rapid rebound in morbidity. Age-dependent acquired resistance to reinfection also developed in subjects chronically exposed to schistosomiasis japonica, suggesting that a vaccine may represent an alternative approach for control of this parasitic infection.

Derivatives of 2-[[N-(Aminocarbonyl)-N-hydroxyamino]methyl]-1,4- benzodioxan as orally active 5-lipoxygenase inhibitors.

N-Hydroxyureas based on the 1,4-benzodioxan template were prepared from appropriately substituted 1,4-benzodioxan-2-methanols as the key intermediates and evaluated in the in vitro guinea pig polymorphonuclear leukocyte 5-lipoxygenase (5-LO) assay for their 5-LO inhibitory activity. Placement of a 7-phenoxy or 7-p-fluorophenoxy substituent resulted in a dramatic increase in in vitro potency. Selected compounds were subsequently assayed in an ex vivo dog model of LTB4 synthesis at a dose of 1.0 mg/kg. The 7-phenoxy derivatives 16 and 17 showed modest duration of action (DA) in this dog model. The 6-regioisomers 21 and 22 were less potent. Replacement of the 7-phenoxy group of 16 with the p-fluorophenoxy moiety enhanced the DA dramatically. Compound 18 (CGS 25667), which had an IC50 value of 100 nM in the in vitro guinea pig 5-LO assay, had a DA of 8.5 h (zileuton, DA = 8.5 h) at the oral dose of 1.0 mg/kg. Optical antipodes (24, 26) of 18 were independently synthesized in high (> 95%) enantiomeric purity from commercially available optically active glycidyl tosylates and evaluated. In the in vitro assay, the 2S-(-)-enantiomer (24, CGS 25997, IC50 = 85 nM) was found to be twice as active as the 2R-(+)-counterpart (26, CGS 25998, IC50 = 180 nM). In the ex vivo experiment, 24, which dose dependently inhibited plasma 5-LO activity, was shown to be significantly longer acting than 26, with a DA of 8.4 h when dosed orally at 1.0 mg/kg.

Impact of annual screening and chemotherapy with praziquantel on schistosomiasis japonica on Jishan Island, People's Republic of China.

The impact of annual screening and treatment with praziquantel on schistosomiasis japonica was examined on Jishan Island in Po Yang Lake, Jiangxi Province. China. Prevalence of infection in the community decreased from 39% in year 1 to 33% in year 3 with a corresponding decrease in the geometric mean egg count from 51 eggs per gram of stool (epg) to 31 epg. The most dramatic changes in infection status and intensity of infection were observed in younger individuals (0-19 years of age). The prevalence of hepatosplenomegaly also significantly decreased, again primarily in younger individuals. No change in the community prevalence of schistosome-induced hepatic fibrosis was observed as determined by ultrasonography. Longitudinal cohort analysis, however, demonstrated significant improvement in treated individuals with advanced hepatic fibrosis. These data indicate that annual screening and treatment had a significant impact on infection status and morbidity and suggest that community therapy may be an effective approach to control schistosomiasis japonica in lake regions and marshlands in China. Further studies are necessary to determine the optimal and most cost-effective approach for drug delivery.

Ebselen is a specific inhibitor of LTB4-mediated migration of human neutrophils.

Ebselen is a seleno-organic anti-inflammatory compound with glutathione peroxidase-like activity that has the unique characteristic of mediating the isomerization of 5-HETE and LTB4 to their biologically inactive trans isomers, both directly in fluid phase and indirectly through metabolic pathways in stimulated peripheral blood leukocytes. LTB4 is an inflammatory mediator with potent chemotactic activity for neutrophilic leukocytes. We studied the effects of ebselen on the chemotactic and chemokinetic responses with human-blood-derived neutrophils. With the use of 120-microns-thick 5-microns-pore durapore filters and low BSA concentrations (0.05%) in the chemotaxis buffers, ebselen was evaluated for its effect on both chemotactic and chemokinetic responses to LTB4, C5a, and fMLP. Ebselen at 3-20 microM concentrations inhibited both chemotactic and chemokinetic responses to optimal concentrations of LTB4 without altering chemotactic responses to C5a or fMLP. Likewise, ebselen at 20 microM specifically inhibited LTB4-stimulated transendothelial migration of neutrophils, while not altering responses to C5a nor fMLP.

Morbidity due to schistosomiasis japonica in the People's Republic of China.

Transmission and morbidity induced by Schistosoma japonicum were evaluated in 825 individuals undergoing periodic treatment with praziquantel on Jishan island, Jiangxi Providence, in the People's Republic of China. Eggs of S. japonicum were found in the stools of 39.4% of the population; 70% of those infected were less than 20 years of age. Hepatomegaly greater than 3 cm in the midsternal line was detected by physical examination and ultrasonography in 75% and 90% of individuals, respectively, regardless of infection status. Symmer's clay pipe-stem fibrosis of the liver was detected by ultrasonography in 20% of all individuals. Hepatitis B surface antigen and antibody to hepatitis C were found in 11% and less than 1% of the population, respectively. Our study suggests that, despite intermittent chemotherapy, morbidity due to S. japonicum is still a significant problem in China.

Ultrastructural localization of a protective 68,000 molecular weight antigen in Schistosoma mansoni.

Vaccination with SMW 68, an Mr 68,000 glycoprotein of Schistosoma mansoni, induces significant protection in mice against challenge schistosome infection. This resistance occurs without the use of adjuvants and without sensitizing animals to granuloma formation. Likewise, passive transfer of monoclonal antibody (MAb) 31-3B6 against SMW 68 confers partial protection against challenge infection. As a first step in understanding how the immune response to this molecule leads to resistance, SMW 68 was localized in three developmental stages of the parasite by immunoelectron microscopy using MAb 31-3B6 and polyclonal antisera raised against purified SMW 68. In cercariae and schistosomula, MAb 31-3B6 bound electron-dense granules within the head gland and similar granules in the preacetabular glands. In adult worms, SMW 68 or related antigens were found to be widely distributed in tissues. Binding of specific antisera was most pronounced in the gut and tegument of male worms, but less so in subtegumental muscles. We conclude that SMW 68 is presented to the immune system in various ways during parasite development. The protective protein or epitope is excreted, and presented on the surface and in the cytoplasm at various stages of the life cycle. The relationship of the location of this protein to its role in protective immunity is discussed.

Dose-finding study for praziquantel therapy of Schistosoma haematobium in Coast Province, Kenya.

To assess the efficacy of low dose praziquantel regimens in comparison with standard 40 mg/kg dosing in the treatment of urinary schistosomiasis, a random allocation dose-finding trial was performed in children and adults from a Schistosoma haematobium endemic region in Coast Province, Kenya. Following an initial screening, 280 individuals with greater than or equal to 50 eggs/10 ml urine were randomly assigned to receive either 10, 20, 30, or 40 mg/kg of the drug in a single oral dose. Two to three months later, cure rates of 26%, 68%, 78%, and 84% were found for the 10, 20, 30, and 40 mg/kg doses, respectively. The results of 10 mg/kg oral dosing were significantly worse than for all other doses in terms of cure rate and of post-treatment prevalence of morbidity. The 40 mg/kg dosing resulted in a significantly higher cure rate than the 20 mg/kg doses; nevertheless, there was no significant difference between 20 mg/kg and 40 mg/kg doses in terms of mean post-treatment intensity of infection or post-treatment prevalence of hematuria or proteinuria. For large-scale control programs, oral 20 mg/kg praziquantel therapy for urinary schistosomiasis may prove as effective as the standard oral 40 mg/kg dosing for control of infection-associated morbidity and reduction of parasite transmission.

Isolation and characterization of a protective antigen for adjuvant-free immunization against Schistosoma mansoni.

A single, 68,000 m.w. glycoprotein antigen from adult Schistosoma mansoni was purified by immunoaffinity chromatography with the use of a newly developed, protective, anti-schistosome murine monoclonal antibody. Immunization with two doses of 0.5 microgram or 1 microgram of purified antigen, without adjuvants, afforded a mean 28% reduction in parasite recovery in CF1 mice, and 2-% reduction in parasite BALB/c mice. On immunoblotting, the 68,000 m.w. antigen was common to S. mansoni adults and schistosomula, whereas parasite eggs contained only cross-reacting low m.w. antigens of 19,100 and 16,000. Immunization resulted in the development of anti-antigen antibody and enhanced immediate cutaneous hypersensitivity to the 31-3B6 antigen. By contrast, delayed-type hypersensitivity and sensitization to circumoval granuloma formation were not observed in immunized mice. It was concluded that the 68,000 m.w. 31-3B6 antigen represents a candidate vaccine for adjuvant-free immunization against S. mansoni.

Discrepancies in outcome of a control program for schistosomiasis haematobia in Fayoum governorate, Egypt.

A large scale mollusciciding and chemotherapy program in the Fayoum area of Egypt was reported to have decreased prevalence of schistosomiasis haematobia from 46% to 7% in approximately 12 years. In order to assess the uniformity of results reported, we have studied the prevalence and intensity of urinary tract disease in a random sample of children aged 6 months-12 years in 3 areas selected on the basis of distance from the main canal supplying Fayoum and where mollusciciding was applied. Only 1 location near the main canal showed low prevalence (2.2%), while in the other 2 areas prevalence was 75.3% and 61.3%. Intensity of infection and disease were significantly more in the latter 2 locations. Following chemotherapy, a marked reduction in prevalence and intensity of infection and reversal of pathology was seen. Since the reported favorable results of the Fayoum project were used to implement a wider control program in southern Egypt, an independent assessment must be included in future plans.

Swamp rice farming: possible effects on endemicity of schistosomiasis mansoni and haematobia in a population in Liberia.

To obtain a better understanding of the possible influence of swamp rice farming on the patterns of Schistosoma mansoni and Schistosoma haematobium infections, the populations of two communities in rural liberia were studied. In one village, Balama (population of 435), swamp rice farms were initiated six years before the survey; in the other nearby community, Gbarta (population of 216), swamp rice farms had not yet been initiated. The prevalence of S. mansoni infection in Balama was 87% vs. 9% in Gbarta (P less than 0.01). The geometric and arithmetic mean egg counts for all infected subjects in Balama were respectively 263 and 671/g feces. in Gbarta, the geometric and arithmetic mean egg counts were 150 and 129/g feces. S. haematobium eggs were detected in 42% of subjects in Balama vs. 11% in Gbarta (P less than 0.01). Hematuria correlated with the presence of S. haematobium eggs in urine. These data indicate that there is a significantly higher prevalence and intensity of schistosomiasis mansoni and haematobia in a community where swamp rice farming has been utilized for 6 years compared to a nearby village where this water irrigation and drainage practice has not yet been implemented.

Morbidity in schistosomiasis japonica in relation to intensity of infection. A study of two rural brigades in Anhui Province, China.

Schistosomiasis japonica remains endemic in several provinces south of the Yangtze River in China because of relatively sparse populations of human beings and dense populations of snails. We studied two brigades in a rural commune in Gui-chi County, Anhui Province, to determine the prevalence, intensity, and morbidity associated with this infection before concerted control efforts were instituted. Quantitative fecal examinations, histories, and physical examinations relevant to schistosomiasis japonica were performed in 96 per cent of the available population 2 to 65 years of age. The prevalence was 26.3 per cent in Brigade A (778 persons) and 14.4 per cent in Brigade B (1532 persons). Clinical symptoms and signs were compared among uninfected persons and persons at three levels of infection as determined by fecal egg output. Some increased weakness was seen only at the heaviest levels of infection; abdominal pain was not an important symptom. Hepatomegaly was somewhat more frequent in moderate and heavy infections, but splenomegaly was rare and unrelated to intensity of infection. Neither stool consistency nor occult blood was related to the presence or intensity of infection. Approximately 50 per cent of the population had been treated for schistosomiasis japonica, 25 per cent repeatedly.

Effect of chronic alcohol intake on hepatic fibrosis and granulomas in murine schistosomiasis mansoni.

In consideration of the vast prevalence of schistosomiasis and heavy alcohol consumption in many parts of the world, the possibility of an interaction between these two conditions inducing liver disease was studied in mice infected with Schistosoma mansoni. Alcohol consumption significantly reduced by 25% the mean granuloma diameter and by about 60% the extent of fibrous tissue deposition determined chemically as hydroxyproline. DNA, as an expression of the inflammatory and cellular components of the granulomatous reaction in the infected animals, was also significantly reduced by alcohol consumption. These results indicate the need for epidemiological studies in the clinical manifestations and course of schistosomiasis in human alcoholics.

Immunopathology of murine infection with Schistosoma mansoni: relationship of genetic background to hepatosplenic disease and modulation.

The influence of genetic factors on the manifestations of disease associated with infection with Schistosoma mansoni (portal hypertension, liver granulomas, hepatosplenomegaly) and their modulation were studied in inbred strains of mice. Three groups were identified according to the degree of portal hypertension: high (portal venous pressure, 19.1 cm H2O: DBA/1J), intermediate (8.9-13.4 cm H2O; BALB/cJ, DBA/2J, CBA/CaJ, C3H/HeJ, and BUB/BnJ), and low responders (6.1 cm H2O; C57BL/6J). Granuloma size, organomegaly, and portal venous pressure were strain dependent and not H-2 dependent and were determined by more than one gene. Studies of schistosomiasis in the F1 generation of high and low responders indicated that more than one gene is involved. Modulation of portal venous pressure between eight and 20 weeks of infection occurred in C57BL/6J but not in BALB/cJ mice and was transferable with immune lymphoid cells. These data indicate that disease associated with infection with S. mansoni and its modulation in mice are influenced by the genetic (non-H-2) background of the host and dependent in part on cell-mediated immunity.