Fetal outcome in obstetric cholestasis Fisk, N M; Storey, G N
British journal of obstetrics and gynaecology,
November 1988, Letnik:
95, Številka:
11
Journal Article
Recenzirano
Obstetric cholestasis has been associated with a high incidence of stillbirth and perinatal complications. Between 1975 and 1984, 83 pregnancies were complicated by cholestasis. Meconium staining ...occurred in 45%, spontaneous preterm labour in 44%, and intrapartum fetal distress in 22%. Of 86 infants two were stillborn and one died soon after birth. Perinatal mortality fell from 107 in a previous series from this hospital (1965-1974) to 35/1000 in this series. Cardiotocography, estimations of oestriol, liver function tests and ultrasonic assessment of amniotic fluid volume failed to predict fetal compromise, whereas amniocentesis revealed meconium in 8 of 26 pregnancies. Early intervention was indicated in 49 pregnancies, 12 because of fetal compromise. This study suggests that intensive fetal surveillance, including amniocentesis for meconium, and induction of labour at term or with a mature lecithin/sphyngomyelin ratio, may reduce the stillbirth rate in this 'high-risk' condition.
The safe and efficient use of herpes simplex virus (HSV)-based vectors to deliver genes of potentially therapeutic benefit to the central nervous system will require their effective disablement by ...the inactivation of viral genes required for lytic growth. Here we report that viruses lacking functional genes for ICP27 (which is required for growth in all cell types) and ICP34.5 (which is required for growth in nondividing cell types) can deliver a marker gene to both the rodent and primate CNS with high efficiency whilst producing relatively minimal damage and having no effect on sodium currents in dorsal root ganglion neurons. Such viruses paradoxically deliver genes at much higher efficiency than the less disabled single mutant lacking ICP34.5 alone and also, as expected, produce less damage in vivo. Moreover, unlike the single mutant lacking ICP27 the double mutant viruses cannot revert to wild-type by acquistion of complimenting gene sequences during growth of virus stocks in vitro on dividing cells expressing ICP27 since artificial expression of ICP34.5 in these cells is not required. Such ICP27-; ICP34.5- viruses thus offer a platform for the development of vectors which are sufficiently safe for ultimate use in human gene therapy.
1
The postjunctional α‐adrenoceptors mediating contractions in the isolated vascular bed of the perfused rat tail have been investigated, in the presence and absence of an increase in perfusion ...pressure by arginine vasopressin (AVP).
2
In the absence of AVP, bolus doses of noradrenaline (NA) and phenylephrine produced pressor responses of similar time course, while UK‐14,304 was practically inactive. Responses to noradrenaline were inhibited more by 0.05 μm prazosin than by 1 μm rauwolscine, suggesting the presence of α1‐adrenoceptors.
3
Following a sustained elevation in perfusion pressure by AVP, both UK‐14,304 and NA (the latter in the presence of 0.05 μm prazosin to inhibit α1‐adrenoceptors) elicited dose‐dependent pressor responses. The maximum response to UK‐14,304 under these conditions was approximately 30% of the maximum response to NA in the absence of prazosin and AVP. Responses to phenylephrine were not affected by the AVP‐induced increase in vascular tone.
4
In the presence of AVP, pressor responses to UK‐14,304 were resistant to 0.05 μm prazosin and susceptible to antagonism by 1 μm rauwolscine (‐log Kb 7.65 ± 0.15). Similarly, responses to NA in the presence of 0.05 μm prazosin and AVP were inhibited by 1 μm rauwolscine. This represents the first demonstration of prazosin‐resistant, rauwolscine‐sensitive α2‐adrenoceptor‐mediated responses in the vasculature of the rat tail.
5
These results suggest that in isolated vascular preparations, functional populations of postjunctional α2‐adrenoceptors may be ‘uncovered’ by the presence of AVP.
More intensive care unit beds are needed Cupples, P A; Makin, A P; McKinnon, S S ...
BMJ. British medical journal (International ed.),
05/1997, Letnik:
314, Številka:
7090
Journal Article
For those patients ineligible for allogeneic bone marrow transplant and who are non-responsive to interferon, autotransplant with peripheral blood stem cells (PBSC) mobilised after intensive ...chemotherapy, may provide a novel approach to improve prognosis in patients with chronic granulocytic leukaemia. PBSC harvests are assessed for CD34-positive cell numbers, which serve as an indicator of engraftment potential, and are also analysed cytogenetically to ascertain tumour cell contamination. However, a more accurate assessment of PBSC harvest contamination requires investigation of the Philadelphia (Ph) status of the CD34pos population, in which the cells that provide long-term engraftment are contained. In this study, we have analysed these levels in mobilised PBSC and also in bone marrow (BM) harvests, taken several weeks prior to mobilising chemotherapy. Using fluorescent in situ hybridisation for the bcr/abl gene fusion, we have shown that the median number of Ph negative cells in CD34pos isolated populations was 14.95% in BM compared to 79.05% in PBSC harvests and that in all PBSC samples tested, Ph positivity in CD34pos populations was always detectable either by FISH or one round PCR methods. In paired assessments of both PBSC and BM harvests, higher levels of Ph negative CD34pos cells (> or = 14%) isolated from BM harvests, taken prior to intensive chemotherapy, correlated with higher levels of Ph negative CD34pos cells (> or = 78.5%) in PBSC harvests. These data may aid in the selection of patients for whom PBSC harvesting, after mobilisation, is more likely to achieve an autograft product containing predominantly Ph negative CD34pos cells and may exclude those patients for whom the risk, morbidity and expense of stem cell harvesting may have no apparent benefit over a chronic phase BM harvest.
Many nuclear hormones have physiological effects that are too rapid to be explained by changes in gene expression and are often attributed to unidentified or novel G protein-coupled receptors. ...Thyroid hormone is essential for normal human brain development, but the molecular mechanisms responsible for its effects remain to be identified. Here, we present direct molecular evidence for potassium channel stimulation in a rat pituitary cell line (GH₄C₁) by a nuclear receptor for thyroid hormone, TRβ, acting rapidly at the plasma membrane through phosphatidylinositol 3-kinase (PI3K) to slow the deactivation of KCNH2 channels already in the membrane. Signaling was disrupted by heterologous expression of TRβ receptors with mutations in the ligand-binding domain that are associated with neurological disorders in humans, but not by mutations that disrupt DNA binding. More importantly, PI3K-dependent signaling was reconstituted in cell-free patches of membrane from CHO cells by heterologous expression of human KCNH2 channels and TRβ, but not TRα, receptors. TRβ signaling through PI3K provides a molecular explanation for the essential role of thyroid hormone in human brain development and adult lipid metabolism.
PDF
