Congenital jaundice in bovine aborted foetuses: an emerging syndrome in southern Belgium.

Southern Belgium faces an unusual recent increase of icteric bovine aborted foetuses. In the necropsy room, the majority of foetuses presented jaundice and splenomegaly. Despite a wide range of analyses, no definitive cause of abortion has yet been established but some analysis results support the leptospirosis hypothesis. This first description of cases will help veterinary practitioners to recognize more cases and to conduct those to the laboratory for future investigations.

Congenital monoblastic leukemia presenting as jaundice, pleural effusion, and ascites: case report and literature review.

Congenital leukemias are a rare group of hematologic neoplasms with a wide range of clinical signs and symptoms. Here we reported a neonate presenting with jaundice, pleural effusion and ascites. The total protein and serum albumin were markedly low at 48 and 12 g/L. Computerized tomography showed the density of liver was asymmetry with several hypoechoic regions. Initial blood routine examination revealed only thrombocytopenia while blood white cells increased to 30.0×10(9)/L with 17% blast cells several days later. Bone marrow biopsy showed the proportion of blasts and promonocytes increased and she was diagnosed as acute monoblastic leukemia.

Autoimmune lymphoproliferative syndrome (ALPS): a case with congenital onset.

We describe a case of autoimmune lymphoproliferative syndrome (ALPS), which is very unusual with regard to a clinical onset soon after birth, and a clinical picture dominated by splenomegaly, jaundice, and consumptive peripheral blood cytopenias, with minimal lymphadenopathy. Our documented close follow up demonstrated initial involvement of the spleen, followed by involvement of the bone marrow and the peripheral blood. The patient underwent bone marrow transplant and is alive and well 20 months after diagnosis.

Delección (mosaico) del cromosoma Y / Delection (mosaic) of chromosome Y

Presentamos el caso de una paciente de 3 meses. Ingresada de recién nacida por ictericia no isoinmune. Soplo sistólico y granuloma umbilical. Oligoamnios. Abuelo paterno con leucemia crónica. Parto al término eutócico, con un peso al nacimiento de 3.720 g. Durante el periodo neonatal es ingresado en la 1ª semana de vida por ictericia (bilirrubina 21 mg/dl). Fue vista por traumatología infantil por pies cavos bilaterales con leve varo. Acude a Cardiología Infantil, a la semana de vida, para estudio de soplo sistólico y por presentar rasgos dismórficos en su fenotipo: fascies tosca. Frente amplia. Sinofidia. Ptosis palpebral. Retronagtia. Tórax: dos mamilas supernumerarias. Auscultación cardiaca: soplo sistolico 1-2/6, no irradiado panfocal sin repercusión hemodinámica. Cariotipo en sangre periférica (cultivo de linfocitos 72 horas estimulados con fitohemaglutinina) con bandas G, muestra dos líneas celulares, una de 46, XY en 6 metafases y otra de 46, X, der. (Y) en 21 metafases. Se aprecia un cromosoma Y de menor tamaño. Estudio de hibridación in situ en sangre periférica (FISH): se ha aplicado la técnica de hibridación in situ fluorescente con la sonda del cromosoma Y, para confirmar que el cromosoma Y diagnosticado mediante bandas G procede del Y (AU)

The Malaysian experience in the typing of genetic variants of alpha-1-antitrypsin.

It is known that alpha1-antitrypsin deficiency is associated with emphysema in adults and liver cirrhosis in neonates. The phenotypes PiZZ and PiSZ are considered to be high risk groups. alpha1-antitrypsin deficiency is one of the most common lethal congenital disorders in Europe and the USA, occurring in approximately 1 in 2,000 caucasians of North European descent. Studies in Malaysia have found that the phenotypes PiZ and PiS are present in our population. Out of 950 samples analyzed, it was found that 10 samples were shown to be apparently Z homozygous phenotype. The phenotype is determined by high resolution isoelectrofocusing on an ultra-thin polyacrylamide gel embedded with narrow range Pi phamarlyte. The isoelectrofocused bands are confirmed by immunofixation and the plasma alpha1-antitrypsin levels determined by electroimmunoassay. The abnormal phenotypes are further confirmed by polymerase chain reaction using allele specific oligonucleotides.

Congenital biliary atresia and jaundice in lambs and calves.

An outbreak of congenital biliary atresia and jaundice is described, in which approximately 300 crossbred lambs and 9 crossbred calves died. The affected animals failed to thrive, developed jaundice and white scours and died within 4 weeks of birth. A common feature of this outbreak and a similar occurrence 24 years previously was the grazing of plants growing on the exposed silt foreshores of Burrinjuck Dam by ewes and cows in the early stages of pregnancy. Epidemiological and pathological findings suggested that a toxic insult to the foetus in early gestation caused choledysgenesis and biliary atresia, leading to diffuse, subacute to chronic cholangiohepatopathy and cirrhosis.

Stereoselectivity of glutathione conjugation: blood elimination of alpha-bromoisovalerylurea enantiomers and biliary excretion of the conjugates in unanesthetized normal or congenitally jaundiced rats.

Stereoselectivity of glutathione conjugation was studied in unanesthetized normal and congenitally jaundiced rats (Groningen Yellow), using the separate enantiomers of alpha-bromoisovalerylurea (BIU) as substrates. The blood elimination half-lives of (R)- or (S)-BIU were 8 and 38 min, respectively. The excretion half-lives of the GSH conjugates in bile in normal rats showed a similar difference: (R)-BIU yielded exclusively (S)-IU-S-G with a T1/2 of 12 min, and (S)-BIU yielded only (R)-IU-S-G with a T1/2 of 36 min. In normal rats 45-47% of the dose of (R)-BIU and (S)-BIU was found in bile as glutathione (GSH) conjugate, and 19-25% was excreted in urine as mercapturates. Similar values in the mutant rats indicated that BIU elimination by GSH conjugation was unimpaired, but the GSH conjugates were absent from bile. In the urine twice as much mercapturates was found as in normal rats. The GSH content and the activity of the glutathione-S-transferases in the liver were similar in mutant and controls. The data on blood elimination of the BIU enantiomers and biliary excretion of the GSH conjugates suggest that for (S)-BIU the conjugation step is rate-limiting, whereas for (R)-BIU a transport step into bile may be rate-limiting.

A serological survey for leptospiral agglutinins among patients in a Barbadian general practice - abstract

Sera from 1,419 patients who attended a Barbadian general practice for a variety of complaints between 1st April and 30th April 1988 were examined for leptospiral agglutinins by the microscopic agglutination test. Sera from patients presenting with pyrexia of unknown origin, jaundice or kidney complaints, and from those whose titre was > 1:400, were also examined by the ELISA for IgM and IgG antibodies. Only one patient was diagnosed clinically as possibly having mild leptospirosis, but three others had been recently infected and some mild cases may have been missed. Altogether, 177 of the patients (12.5 percent) were positive at titres> 1:50. These were 104 of the 739 males (14 percent) and 73 of the 680 females (11 percent) (no statistically significant difference). Seropositivity tended to increase with age (p<0.01), and the highest rates were in agricultural workers (35 percent), labourers (24 percent) and non-manual outdoor workers (19 percent). The difference in seropositivity between the various indoor and outdoor occupational groups was highly significant (p<0.005). Autumnalis (31 percent of the sero postives), Panama (15 percent), Australia (14 percent) and Pyrogenes (11 percent) were the serogroups most commonly recorded among the seropositive patients. Autumnalis predominated in each of the main occupational groups except indoor non-manual workers where Panama, Pyrogenes and Australis occurred more frequently. Ninety-five per cent of the positive titres ranged between 1:50 and 1:400. Titres tended to increase with age, but there was no obvious association between higher titres and particular occupations (AU)

Unconjugated bilirubin and the bile from light exposed Gunn rats inhibit intestinal water and electrolyte absorption.

Jaundiced babies undergoing phototherapy often develop diarrhoea. The cause of it is still uncertain. Increasing evidence supports a role of a secretory mechanism for the diarrhoea. We therefore studied the effects of bile from congenitally jaundiced rats undergoing phototherapy and of unconjugated bilirubin on rat small intestine in vivo and in vitro. Results suggest that: (1) the bile from homozygous Gunn rats under phototherapy has an anti-absorptive effect when tested in the perfused jejunum of normal Wistar rats; (2) unconjugated bilirubin has a dose dependent secretory effect on the intestinal transport of water and electrolytes, when tested in the same system. Alteration of cyclic AMP or cyclic GMP, known intracellular mediators of secretion, was not observed. We conclude that free bilirubin is an intestinal secretagogue acting by an as yet unknown mechanism, that may mediate the secretory type of diarrhoea in jaundiced neonates undergoing phototherapy.

Increase in a specific cytochrome P-450 isoenzyme in the liver of congenitally jaundiced Gunn rats.

Congenitally jaundiced (jj) Gunn rats had a greater hepatic microsomal content of a cytochrome P-450 isoenzyme, P-450c, than did the non-jaundiced (Jj) rats. No differences in content of P-450b, P-450d and pregnenolone-16 alpha-carbonitrile-induced (PCN) P-450 were found between jj and Jj rats. This is the first demonstration of a constitutive increase in a specific cytochrome P-450 isoenzyme in association with a genetic defect.

Congenital jaundice in rats due to the absence of hepatic bilirubin UDP-glucuronyltransferase enzyme protein.

Three major UDP-glucuronyltransferase isoenzymes (50-54 kDa) have been identified by immunoblot analysis. Bilirubin UDP-glucuronyltransferase (54 kDa) was specially induced by treatment of the rats with clofibrate. This isoenzyme was not detectable in liver microsomal extracts from congenitally jaundiced Gunn rats and was not induced by treatment of these animals with clofibrate. Phenol UDP-glucuronyltransferase, the only isoenzyme determined to be present in foetal Wistar rat liver microsomes was not detected by enzyme assay or immunoblot analysis of foetal Gunn rat liver microsomal extracts. These results provide the first indication that bilirubin UDP-glucuronyltransferase and possible phenol UDP-glucuronyltransferase proteins are not present in the congenitally jaundiced Gunn rat.

Haemolytic anaemia in the Gunn rat following transplantation of isolated hepatocytes injected with Haemobartonella muris.

Extensively purified preparations of isolated rat hepatocytes derived from Wistar rats infected with Haemobartonella muris induced haemolytic anaemia when injected into congenitally jaundiced Gunn rats. In the absence of overt parasitaemia and marked falls in haematocrit, elevation of total plasma bilirubin levels was a valuable indicator of red-cell destruction. Evidence is presented that the parasite is removed by the spleen from the surface of infected red cells which then remain in the circulation.

An explanation for the reduction in bilirubin levels in congenitally jaundiced Gunn rats after transplantation of isolated hepatocytes.

Isolated hepatocytes prepared from Wistar rats by mechanical means were infused into the liver of congenitally jaundiced Gunn rats. Red cell survival was determined in the recipients and their total plasma bilirubin was measured just before and 20 days after transplantation. Similar measurements were made in transplanted Gunn rats receiving the immunosuppressant drug cyclophosphamide at 5 mg/kg/day and in a group of splenectomized Gun rats. Red cell survival was significantly prolonged in all transplanted rats and in the splenectomised group. Total plasma bilirubin also fell significantly in all three groups by up to 25%, a change we attribute to reduced red cell turnover, haemoglobin synthesis and hence reduced bilirubin synthesis. Blockade of the splenic reticuloendothelial system by hepatocyte debris is suggested as a possible cause.

Effect of phototherapy on serum bilirubin levels and red blood cell survival in congenitally jaundiced Gunn rats.

Although phototherapy with blue fluorescent light effectively lowered the serum bilirubin concentration in congenitally jaundiced Gunn rats, no effect on red blood cell surivival as determined by chromium-51 labeling of homologous red blood cells and carboxyhemoglobin concentration was observed. Furthermore, attempts to demonstrate metabolic stress to the red blood cells failed to show increased glucose consumption. No oxidant damage to red cells as reflected by methemoglobin production and Heinz body formation was observed. Thus the anticipated hemolysis secondary to oxidant damage to red blood cells from phototherapy was not found.

The displacement of bilirubin from albumin by furosemide.

Since furosemide, a sulfonamide diuretic, has been recommended for use in the newborn infant, a study was made of its effect on the bilirubin-binding capacity of albumin. Furosemide was compared to sulfisoxazole, a known displacer of bilirubin, by means of three methods. First, aliquots of whole blood from 20 icteric infants were diluted in phosphate buffer along with expected clinical concentrations of furosemide and sulfisoxazole. The red cells and globulins were then isolated and bilirubin concentrations were measured in these two fractions. The addition of Furosemide resulted in the displacement of bilirubin from albumin to red cells and globulins. Mole for mole, furosemide displaced bilirubin about as well as sulfisoxazole. Second, the hydroxybenzeneazobenzoic acid dye binding test of Porter and twaters was performed using the sera of eight jaundiced newborn infants. The mean dye binding capacity of the sera was significantly reduced with the addition of furosemide to a final concentration of 2 mug/ml. Third, the administration of furosemide (5 mg/kg) or sulfisoxazole (50 mg/kg) to adult Gunn rats resulted in a significant fall in mean serum bilirubin concentration compared to saline controls. Furosemide, like sulfisoxazole, is a potent displacer of bilirubin and should be used with caution in jaundiced infants.

[Jaundice associated with congenital hypertrophic pyloric stenosis (author's transl)]. / Ictericia asociada a estenosis hipertróifica de píloro

The clinical and biological findings in six infants with congenital hypertrophic pyloric stenosis with associated jaundice are described. Pathogenesis of this association is not known but current hypothesis are based on either a decrease in the activity of hepatic glucuronyl transferase or an increase in the activity of intestinal glucuronidase. Correction of dehydration and alkalosis does not modify the hyperbilirubinemia which only disappears after pyloromiotomy.