Sulfur mass-independent fractionation in subsurface fracture waters indicates a long-standing sulfur cycle in Precambrian rocks.

The discovery of hydrogen-rich waters preserved below the Earth's surface in Precambrian rocks worldwide expands our understanding of the habitability of the terrestrial subsurface. Many deep microbial ecosystems in these waters survive by coupling hydrogen oxidation to sulfate reduction. Hydrogen originates from water-rock reactions including serpentinization and radiolytic decomposition of water induced by decay of radioactive elements in the host rocks. The origin of dissolved sulfate, however, remains unknown. Here we report, from anoxic saline fracture waters ∼2.4 km below surface in the Canadian Shield, a sulfur mass-independent fractionation signal in dissolved sulfate. We demonstrate that this sulfate most likely originates from oxidation of sulfide minerals in the Archaean host rocks through the action of dissolved oxidants (for example, HO· and H2O2) themselves derived from radiolysis of water, thereby providing a coherent long-term mechanism capable of supplying both an essential electron donor (H2) and a complementary acceptor (sulfate) for the deep biosphere.

Endogenous cellulase production in the leaf litter foraging mangrove crab Parasesarma erythodactyla.

The sesarmid crab Parasesarma erythodactyla consumes large amounts of mangrove leaf litter but its biochemical capacity for cellulose digestion is poorly known. We demonstrate the presence of endo-ß-1,4-glucanase, ß-glucosidase and total cellulase activities in the digestive juice of this crab. The highest total cellulase activity was observed at mildly acidic pH (5 to 6) and temperature between 30 and 50°C. A 1752bp cDNA containing an open reading frame of 1386bp encoding a putative endo-ß-1,4-glucanase (EG) of 461 amino acids was identified in the crab's hepatopancreas using polymerase chain reaction (PCR), cloning and sequencing techniques. P. erythodactyla endo-ß-1,4-glucanase (PeEG) contains a glycosyl hydrolase family 9 (GHF9) catalytic domain with all catalytically important residues conserved, and shows high sequence identity to GHF9 EGs reported from other arthropods. The endogenous origin of PeEG was confirmed by PCR amplification of a ~1.5kb DNA fragment, containing a phase 1 intron flanked by two exon sequences identical to the cDNA, from genomic DNA isolated from the crab's muscle tissue. PeEG encoding cDNA is the first endogenous EG sequence reported from the brachyuran crabs. Using degenerate primers, we also isolated 204bp cDNA fragments with sequences affiliated to EG from the hepatopancreas of eight other mangrove crabs of the Sesarmidae (Neosarmatium trispinosum and Sesarmoides borneensis), Macrophthalmidae (Ilyograpsus daviei, Australoplax tridentata, and Macrophthalmus setosus), Varunidae (Pseudohelice subquadrata), Heloeciidae (Heloecius cordiformis), and Ocypodidae (Uca perplexa) families, suggesting that endogenous cellulase production may be a common characteristic among the detritivorous mangrove crabs.

Long-term somatic follow-up of prenatally treated children with congenital adrenal hyperplasia.

Prenatal virilization of female fetuses is a serious symptom associated with severe congenital adrenal hyperplasia. In attempt to avoid sexual ambiguity, prenatal treatment of 21-hydroxylase deficiency was initiated in 1984, with the first Scandinavian case treated in 1985. Here we have studied the outcome of prenatal diagnosis and therapy of 44 at-risk pregnancies monitored during the years 1985-1995 in Scandinavia. Treated mothers and children were compared with matched controls. Compared to their elder affected sisters, all 5 girls with severe congenital adrenal hyperplasia who were treated until term showed little virilization. Only 1 required surgery for labial fusion. The majority of the 44 dexamethasone-treated fetuses demonstrated normal pre- and postnatal growth compared to matched controls. However, several adverse events such as failure to thrive and delayed psychomotor development, were reported among the treated infants. In addition, treated mothers reported more side-effects during pregnancy than did controls. A significant increase in weight gain was observed during early pregnancy when treatment was initiated, but this initial rapid weight gain declined during late pregnancy or when treatment was terminated. Thus, experience to date suggests that prenatal treatment of affected female fetuses is generally efficient in minimizing virilization of external genitalia. However, there is still a need to collect more data concerning possible rare unfavorable effects of this therapy on mother and child.

Prenatal diagnosis in Sweden: organisation and current issues.

Invasive prenatal diagnosis was introduced in Sweden in the early 1970s and is an integral part of the public health care system. Funding is provided by taxation; the patient only pays a consultation fee. Genetic analyses on a broad range of cytogenetic and molecular disorders are performed at the 6 university-affiliated hospitals and in 1 county hospital. About 6% of all newborns have been cytogenetically screened during pregnancy, and about 90% of the analyses are performed after amniocentesis. The main indication is chromosome analysis because of advanced maternal age.

Lack of evidence of permanent engraftment after in utero fetal stem cell transplantation in congenital hemoglobinopathies.

The use of fetal hematopoietic stem cells for in utero transplantation to create permanent hematochimerism represents a new concept in fetal therapy. In one fetus with alpha-thalassemia, one with sickle cell anemia, and one with beta-thalassemia, we have transplanted fetal liver cells obtained from legal abortions in gestational weeks 6-11. The fetus with alpha-thalassemia was transplanted twice during pregnancy, in the 15th (20.4 x 10(8) cells/kg) and in the 31st weeks of gestation (1.2 x 10(8) cells/kg), and is now two years of age. One fetus with sickle cell anemia received its transplant in the 13th week of gestation (16.7 x 10(8) cells/kg), and is now one year old. The fetus with beta-thalassemia was transplanted in 18th week (8.6 x 10(8) cells/kg), and is now three months old. Engraftment was evaluated by chromosomal analysis (sex chromosomes), red cell phenotyping, HLA class I and II typing, and PCR (polymerase chain reaction) for Y chromosome-specific sequences and DNA polymorphisms in cord and peripheral blood. The children with alpha- and beta-thalassemia underwent bone marrow aspirations at 3 and 7 months of age, respectively. In neither of these cases were we able to detect convincing evidence of stem cell engraftment. Thus, the administration of fetal stem cells to fetal recipients after the 12th week of gestation did not result in permanent hematochimerism. It remains to be determined whether the engraftment process can be promoted by earlier transplantations and/or higher cell doses.

Monosomy 1p36.31-33-->pter due to a paternal reciprocal translocation: prognostic significance of FISH analysis.

A rare monosomy 1p36.31-33-->pter was found in a child with physical anomalies, psycho-motor retardation, and seizures. Cytogenetic investigation suggested an unbalanced translocation between 1p and an acrocentric chromosome, but the rearrangement was difficult to assess accurately using conventional chromosome banding techniques. The half-cryptic translocation was further characterized using fluorescence in situ hybridization, and the aberrant chromosome 1 was shown to be a derivate of a paternal reciprocal translocation t(1;15) (p36.31-33;p11.2-12). The breakpoints on chromosome 1 and 15 were defined in detail using locus specific probes. The rearrangement did not include the region on chromosome 1p which previously has been suggested to predispose to the development of neuroblastoma in a case with a constitutional translocation. At 3 6/12 years, the patient has no clinical signs of this disease, which illustrates the prognostic significance of this investigation.

Direct and inverted reciprocal chromosome insertions between chromosomes 7 and 14 in a woman with recurrent miscarriages.

We present the first case of direct and inverted reciprocal chromosome insertions between human chromosomes 7 and 14, ascertained because of repeated spontaneous abortions. Prometaphase GTG banding analysis showed the karyotype to be 46, XX, inv ins (7;14)(7pter-->7q11.23::14q32.2-->14q 22::7q21.2-->7qter), dir ins(14;7)(14pter-->14q 22::7q11.23-->7q21.2::14q32.2-->14qter). Origins of the insertion have been confirmed by chromosome painting with libraries specific for chromosomes 7 and 14 using fluorescence in situ hybridization.

In utero haematopoietic stem cell transplantation: current perspectives and future potential.

In utero transplantation (IUT) of haematopoietic cells is a new therapeutic option for families with increased risk of having a child with an inherited disorder. Immunological naiveté and the rapidly expanding haematopoietic system in the first trimester human fetus, make therapeutic intervention by IUT a real possibility for those disorders which can be diagnosed early in gestation. Fewer cells are required than in postnatal BMT and therapy can be offered before the pathological sequelae of a disorder become manifested. However, only a few cases of IUT have been performed in humans and it is imperative that consensus is reached quickly on issues such as cell numbers/cell types so that the benefits of this approach to treatment can be realised. This review presents the current status of IUT, the cases thus far recorded and offers a prospective view of developments in this rapidly expanding area.

Concentrations of mercury, cadmium and lead in brain and kidney of second trimester fetuses and infants.

The concentrations of mercury (Hg), cadmium (Cd) and lead (Pb) in brain (cerebrum) and kidney during fetal (second trimester terminations or abortions, n = 20) and postnatal (infants deceased before three months of age, n = 15) development have been studied. Information on possible sources of exposure was obtained from the mothers of the fetuses, but not from those of the infants. The median concentration of Hg in the brain was 4 micrograms/ kg wet weight in both fetuses and infants (total range < or = 2-23 micrograms/kg). The concentrations of Hg in the kidneys were significantly higher than in brain, median of Hg 6 micrograms/kg (range < or = 5-34 micrograms/kg) in fetuses and 10 micrograms/kg (< or = 7-37) in infants. There was a tendency of increasing concentration of Hg in the fetal kidney, but not in the brain, with increasing number of amalgam fillings in the mothers. The concentration of Cd in the brain was less than 1 microgram/kg in most cases, both in fetuses and infants. The concentration of Cd in the kidneys was significantly higher, with a median of about 2 micrograms/kg (1-8 micrograms/kg) in both groups. There was no detectable association between tissue Cd concentrations and the smoking habits of the mothers. The concentration of Pb in brain was below 10 micrograms/kg in most cases. In the kidneys, the concentrations of Pb were significantly higher, with a median of 12 micrograms/kg in the fetuses (range < or = 6-20 micrograms/kg) and 15 micrograms/kg (< or = 9-36 micrograms/kg) in the infants. In general, the concentrations of Cd and Pb were lower than in previously reported studies.

Second-trimester biochemical screening.

The past years have seen considerable progress in the area of biochemical screening. Increasing data have now clearly shown the advantages of multiple markers, particularly beta-hCG over AFP alone. There continues to be considerable controversy over the best mathematic algorithm and which markers are best (e.g., beta-HCG, uE3, and so forth). There seems to be a plateau of detection frequencies at about 65% to 70% with current methodologies. Further work needs to be done, however, including some new approaches, if there is to be substantial improvement of screening sensitivity. The combination of biochemical with biophysical parameters as discussed elsewhere in this issue represents the next level of sophistication in the attempt to identify the highest proportion of abnormalities with the fewest false-positives.

Concentrations of copper, zinc and selenium in brain and kidney of second trimester fetuses and infants.

The concentrations of copper (Cu), zinc (Zn) and selenium (Se) in the brain and kidneys of second trimester fetuses (abortion cases) and infants (deceased before three months of age) were determined. Concentrations of Cu in brain, 0.31-1.6 mg/kg wet weight, increased with age, and were, on the average, three times higher in the brains of infants than of fetuses. In kidneys, Cu concentrations ranged between 0.34 and 2.9 mg/kg, and increased with age after birth. Concentrations of Zn in the brain decreased significantly with age in the fetuses, from about 7 mg/kg at post-conceptional week 12 to less than 5 mg/kg at week 20, but increased again postnatally. In kidneys, Zn concentrations (12-37 mg/kg) increased in parallel with the increase in tissue density. Concentrations of Se in brain, 0.072-0.14 mg/kg, decreased with age in the fetuses, but increased with age postnatally. Kidney Se concentrations (0.16-0.55 mg/kg) did not change significantly with age during the fetal period, but increased about 2.5 times during the postnatal period. There was a significant association between the concentrations (on molar basis) of Zn and Cu in kidneys, but not in brain. There was no correlation between the concentrations of Cu, Zn or Se and those of mercury, cadmium and lead, previously determined in the same samples, with the exception of mercury and Se in kidneys.

Successful EXIT (ex utero intrapartum treatment) procedure in a fetus diagnosed prenatally with congenital high-airway obstruction syndrome due to laryngeal atresia.

Congenital high-airway obstruction syndrome (CHAOS) is due to rare malformations and has been reported previously in only few cases. If the diagnosis can be made prenatally, the ex utero intrapartum treatment (EXIT) procedure may be life-saving. A healthy 28-year old nulli-para was referred because of isolated ascites found at gestational week 16 during routine ultrasound scan. Repeated scans showed overdistended hyperechogenic lungs with inverted diaphragm and a dilated trachea, which was interpreted as a CHAOS resulting from laryngeal atresia. The ascites eventually disappeared. An EXIT procedure was performed at 35 weeks of gestation. Anesthesia of the mother was induced with thiopental, succinylcholine and fentanyl followed by intubation, and maintained with isoflurane and nitrous oxide. A low abdominal midline incision was performed followed by a low transverse incision of the uterus. The fetal head, right arm and shoulder were delivered and intramuscular anesthesia was administered to the fetus. Immediate laryngoscopy confirmed the diagnosis and a tracheostomy was therefore performed. Surfactant was given after a few minutes of ventilation. Compliance improved and when the fetus was easy to ventilate, it was delivered. The baby is developing normally at 18 months of age. Surgical correction of the malformation will be performed after two years of age. It is concluded that some fetuses with a prenatal diagnosis of CHAOS can benefit from the EXIT procedure at delivery. This necessitates a multidisciplinary management team.

[Twin-twin transfusion syndrome--front line in fetal medicine]. / Tvilling--tvillingtransfusionssyndrom--frontlinje i fostermedicin.

Twin-twin transfusion develops in 10-20% of monochorionic twin pregnancies. As far as we know the underlying disturbance is an unbalanced anastomosis between the two fetuses on the placental surface. Without treatment mortality is as high as 80% if diagnosed before viability. One of this article's authors spent two months in Hamburg at the 'Allgemeine Krankenhaus', Barmbeck in Germany and describes the technique used there to coagulate these anastomoses via fetoscope. The outcome seems very promising with overall survival of 80% using this method. In the article pathogenesis and alternative treatments are also discussed.

[Prenatal diagnosis and treatment of adrenogenital syndrome. Prevent virilization of female fetuses]. / Fostermedicin. Prenatal diagnostik och behandling av adrenogenitalt syndrom. Förhindra virilisering av flickfoster.

Congenital adrenal hyperplasia (CAH) is the common name of a constellation of diseases that impair cortisol synthesis in the adrenal cortex. As defects in each of three steroidogenic enzymes, 21-hydroxylase, 11 beta-hydroxylase, and 3 beta-hydroxysteroid dehydrogenase, promote overproduction of adrenal androgens, affected female fetuses may be virilised. The major cause of CAH is 21-hydroxylase deficiency, the incidence of which is 1:10,000 live births in the Swedish population. Of the 10-15 children born in Sweden each year with 21-hydroxylase deficiency, 3-5 will be virilised girls who must undergo traumatic surgery of the external genitalia. This can be prevented by administration of dexamethasone to the gravida during pregnancy. Prenatal treatment was introduced in Sweden in 1985, prenatal diagnosis being based in most cases on direct mutational analysis using allele-specific PCR on DNA from chorionic villus samples. In our experience, genotype corresponds well to phenotype, and we recommend that all children with 21-hydroxylase deficiency be genotyped in order to prepare the family for rapid and reliable prenatal diagnosis and possible treatment when the next child is awaited. Since 1985, 35 women have received prenatal treatment in Sweden, six of the 35 fetuses being found to be affected females and treated until term. As compared with their older sisters, all of these six girls were characterised by no signs, or only minor signs, of virilisation, and only one required surgery because of labial fusion and recurrent urinary tract infections. As a group, the 35 infants were characterised by normal birth weight and length, and normal growth during the first year of life. Passage of developmental milestones was normal though several adverse events, both in treated mothers and infants, have been reported. Approximately one fourth of the women treated throughout pregnancy reported some side-effect (e.g., excessive weight gain, severe cutaneous striae, mood fluctuations and irritability, acne and hirsutism, or oedema). One unaffected boy, treated for seven weeks, was born with severe hydrocephalus and agenesis of the corpus callosum; two affected sisters and one unaffected girl were characterised by failure to thrive during the first year of life, but later recovered (one of the affected sisters was later diagnosed as suffering from mitochondrial disease). Although in our experience prenatal treatment with dexamethasone is effective in preventing virilisation of girls with 21-hydroxylase deficiency, some adverse events have been noted in treated infants. As it remains unknown whether these events were attributable to the treatment, it must still be regarded as experimental, and its use should be centralised and meticulously monitored until more experience has been gained.

[Minimally invasive techniques make fetal surgery possible. Disabling abnormalities can be corrected]. / Minimalinvasiv teknik gör kirurgi på foster möjlig. Handikappande missbildningar Kan korrigeras.

Increases in our knowledge of the fetus and improved skill in early prenatal diagnosis inevitably result in attempts to treat some of the abnormalities detected. Although most fetal malformations diagnosed prenatally in continuing pregnancies are best managed by medical and surgical intervention after planned delivery, some structural defects may require in utero-treatment to forestall subsequent sequelae. The article consists in a review of the current status of ultrasound-guided invasive fetal therapy, including multifetal pregnancy reduction, manipulation of amniotic fluid, drainage and shunting procedures, fetal transfusion therapy, operative fetoscopy, and in utero stem cell transplantation. Future prospects and developments in this rapidly expanding field are also outlined.

[Folic acid protects against neural tube defects. But how many women of reproductive age have been informed about this fact?]. / Folsyra skyddar mot neuralrörsdefekter. Men hur många kvinnor i fertil ålder har fått information om detta?

The involvement of folic acid in the aetiology of neural tube defects (NTDs) has been discussed for decades. Both observational and controlled intervention trials have shown periconceptional folic acid supplementation (PFAS) to significantly reduce the incidence both of first-time and recurrent NTDs. PFAS may also be associated with reduction in the incidence of certain other congenital malformations, preterm delivery, and intra-uterine growth retardation. However, the mechanism whereby folic acid exerts its protective effect remains unclear. Thermolabile 5,10-methyl-enetetrahydrofolate reductase was the first folate-related enzyme to be associated with an increased risk of NTDs. This genetic variant may result in increased plasma homocysteine levels, which have been linked to an increased risk of NTDs. The folate-dependent genetic variants known today can explain no more than 30-50 per cent of the observed protective effect of folate. However, available evidence suggests low maternal folate status itself to be the major determinant of NTD risk. Since the vast majority of NTDs are first occurrences, and in Sweden a large proportion of fetuses with spina bifida remain undetected at routine ultrasonography during pregnancy, primary prevention by means of PFAS represents a major potential public health asset, capable of reducing both mortality and morbidity due to NTDs. Accordingly, implementation of a national strategy to reduce the incidence of NTDs, and promote awareness among health care providers and women of reproductive age of the benefits of PFAS is strongly to be recommended. Although supplemental folic acid tablets are the best proven means of improving folate status, compliance may be a problem, which emphasises the importance of considering a nutrient fortification programme as a complementary strategy for reducing the incidence of NTDs.

[Successively improved prognosis in erythrocyte immunization]. / Successivt förbättrad prognos vid erytrocytimmunisering.

Prognosis in cases of erythrocyte immunisation has improved continuously over the past decades. Morbidity and mortality have been reduced by improvements in management, including screening programmes, non-invasive ultrasound evaluation and invasive procedures. The article provides an outline of the latest developments in the management of erythrocyte immunisation, and several controversial issues are discussed, such as antibody screening, strategies for the reduction of antibody titres, and the organisation of care.

[Twin-twin transfusion syndrome--front line in fetal medicine]. / Tvilling-tvillingtransfusionssyndrom--frontlinje i fostermedicin.

Twin-twin transfusion develops in 10-20% of monochorionic twin pregnancies. As far as we know the underlying disturbance is an unbalanced anastomosis between the two fetuses on the placental surface. Without treatment mortality is as high as 80% if diagnosed before viability. One of this article's authors spent two months in Hamburg at the "Allgemeine Krankenhaus", Barmbeck in Germany and describes the technique used there to coagulate these anastomoses via fetoscope. The outcome seems very promising with overall survival of 80% using this method. In the article pathogenesis and alternative treatments are also discussed.