Changes in the concentration of 17 alpha,20 alpha-dihydroxypregn-4-en-3-one during pregnancy, labor, and delivery and the effect of dexamethasone treatment during the third trimester of pregnancy

To study whether an alteration of placental steroid metabolism occurs during human pregnancy similar to that in the ewe, we measured the concentration of 17 alpha,20 alpha-dihydroxypregn-4-en-3-one (17,20 alpha-OHP) in peripheral plasma. As the pregnant ewe nears term, the utero-ovarian venous concentrations of 17,20 alpha-OHP increase, suggesting induction of placental 17 alpha-hydroxylase. The mean plasma concentration of 17,20 alpha-OHP measured by RIA in normal menstruating women was 1.1 +/- 0.12 (+/- SE) ng/ml. Similar values were found in plasma from ovariectomized women. In the first and second trimesters of pregnancy, the plasma values of 17,20 alpha-OHP were not significantly different from those in the nonpregnant women, while in the third trimester, the mean plasma concentration was significantly increased (mean +/- SE, 2.6 +/- 0.3 ng/ml). The plasma concentration of 17,20 alpha-OHP was studied in 15 women in late pregnancy, during labor, at delivery, and postpartum. The concentration increased during labor as delivery approached and reached a maximum at the time of delivery, ranging from 4.1-11.2 ng/ml, followed by a significant decrease within 1-4 h postpartum. The mean (+/- SE) 17,20 alpha-OHP concentrations in the venous and arterial cord blood were 8.7 +/- 1.6 and 5.8 +/- 2.0 ng/ml, respectively. To study the effect of increased circulating level of corticosteroids on the serum concentration of progestins, 74 women with premature labor with or without premature rupture of membranes were treated with either placebo or 4 im injections of dexamethasone phosphate (5 mg each) at 12-h intervals. Blood samples were drawn at 0, 14, 26, and 46 h, approximately 2 h after each dexamethasone dose. Plasma progesterone, 17 alpha-hydroxyprogesterone (17-OHP), and 17,20 alpha-OHP values at zero time were 140 +/- 15.8 (+/- SE; n = 21), 7.8 +/- 1.5 ng/ml (n = 16), and 2.3 +/- 0.3 ng/ml (n = 20), respectively. In patients treated with dexamethasone, the plasma progesterone values tended to increase at 14, 20, and 46 h, but 17-OHP and 17,20 alpha-OHP values decreased significantly compared to levels in placebo-treated patients. In conclusion, the concentration of plasma 17,20 alpha-OHP increased during the third trimester of pregnancy, and the increment continued through labor and delivery. During antenatal dexamethasone administration, progesterone in the maternal circulation tended to increase, while 17-OHP and 17,20 alpha-OHP decreased significantly. In the human, in contrast to the ewe, dexamethasone treatment in the third trimester does not appear to stimulate placental 17 alpha-hydroxylase activity.     

Growth hormone-releasing factor analogue (hGRF1-29NH2): immunoreactive-GRF plasma levels after intravenous and subcutaneous administration

A homologous radioimmunoassay (RIA) system for human growth hormone-releasing factor 1-29NH2 (hGRF 1-29-NH2) was developed and applied to the measurement of immunoreactive (IR) concentrations of the peptide in anaesthetized rats to determine some of its pharmaco-kinetics after i.v. and s.c. administration. Analysis of the biphasic disappearance curve of IR-hGRF-1-29NH2 from plasma after i.v. injection (10 micrograms) gave values for the half-lives of the initial distribution phase (alpha) and for the elimination phase (beta) of 1.9 +/- 0.2 min and 10.4 +/- 0.2 min respectively. There was rapid uptake of the peptide from the site of s.c. injection but comparison of areas under the plasma IR-hGRF1-29NH2/time curves showed that the estimated total amount in the circulation after s.c. injection was only 4% of that obtained after i.v. administration. A large degree of degradation of the peptide is indicated either at the site of injection or during transfer to plasma; this susceptibility to rapid breakdown is reflected in the short half-life of the peptide in the circulation. Therefore the measurement of the above parameters is a prerequisite when assessing potency of GRF analogues in-vivo and when implementing suitable dosage regimens for clinical purposes.     

Amphotropic or Gibbon Ape Leukemia Virus Retrovirus Binding and Transduction Correlates with the Level of Receptor mRNA in Human Hematopoietic Cell Lines

ABSTRACT: The low level of amphotropic retrovirus mediated gene transfer into human hematopoietic stem cells (HSC) has been an impediment to gene therapy for hematopoietic diseases (1). We have previously shown that mouse and human HSC have low levels of the mRNA encoding PiT-2, the amphotropic retrovirus receptor. We hypothesized that the low level of PiT-2 mRNA was responsible for the low frequency of transduction of HSC by amphotropic retroviral vectors (2). In this study we compared the level of PiT-2 and PiT-1, the Gibbon Ape Leukemia Virus receptor (GaLV), in 5 human tissue culture cell lines. PiT-2 and PiT-1 mRNA levels were highest in K562 cells and lowest in HL60 cells. In hematopoietic cell lines, the level of PiT-2 or PiT-1 mRNA correlated directly with retrovirus binding and transduction with the appropriate (amphotropic or GaLV) retrovirus vector. The level of expression of PiT-2 and PiT-1 mRNA could be increased by treatment of HL60 cells with either PMA or Interleukin-1α. The increase in the level of PiT-2 and PiT-1 mRNA correlated with increased transduction with both amphotropic and GaLV retroviral vectors. We conclude that the improved transduction was a direct effect of the increased levels of receptor mRNA and unrelated to changes in the cell cycle status.     

Supported discharge service versus inpatient care evaluation (SITE): a randomised controlled trial comparing effectiveness of an intensive community care service versus inpatient treatment as usual for adolescents with severe psychiatric disorders: self-harm,functional impairment,and educational and clinical outcomes

Clinical guidelines recommend intensive community care service treatment (ICCS) to reduce adolescent psychiatric inpatient care. We have previously reported that the addition of ICCS led to a substantial decrease in hospital use and improved school re-integration. The aim of this study is to undertake a randomised controlled trial (RCT) comparing an inpatient admission followed by an early discharge supported by ICCS with usual inpatient admission (treatment as usual; TAU). In this paper, we report the impact of ICCS on self-harm and other clinical and educational outcomes. 106 patients aged 12–18 admitted for psychiatric inpatient care were randomised (1:1) to either ICCS or TAU. Six months after randomisation, we compared the two treatment arms on the number and severity of self-harm episodes, the functional impairment, severity of psychiatric symptoms, clinical improvement, reading and mathematical ability, weight, height and the use of psychological therapy and medication. At six-month follow-up, there were no differences between the two groups on most measures. Patients receiving ICCS were significantly less likely to report multiple episodes (five or more) of self-harm (OR = 0.18, 95% CI: 0.05–0.64). Patients admitted to private inpatient units spent on average 118.4 (95% CI: 28.2–208.6) fewer days in hospitals if they were in the ICCS group compared to TAU. The addition of ICCS to TAU may lower the risk of multiple self-harm and may reduce the duration of inpatient stay, especially in those patients admitted for private care. Early discharge with ICCS appears to be a viable alternative to standard inpatient treatment.

     

Aggressive spinal haemangiomas: imaging correlates to clinical presentation with analysis of treatment algorithm and clinical outcomes

Objective:

Aggressive spinal haemangiomas (those with significant osseous expansion/extraosseous extension) represent approximately 1% of spinal haemangiomas and are usually symptomatic. In this study, we correlate imaging findings with presenting symptomatology, review treatment strategies and their outcomes and propose a treatment algorithm.

Methods:

16 patients with aggressive haemangiomas were retrospectively identified from 1995 to 2013. Imaging was assessed for size, location, CT/MR characteristics, osseous expansion and extraosseous extension. Presenting symptoms, management and outcomes were reviewed.

Results:

Median patient age was 52 years. Median size was 4.5 cm. Lumbar spine was the commonest location (n = 8), followed by thoracic spine (n = 7) and sacrum (n = 2); one case involved the lumbosacral junction. 12 haemangiomas had osseous expansion; 13 had extraosseous extension [epidural (n = 11), pre-vertebral/paravertebral (n = 10) and foraminal (n = 6)]. On CT, 11 had accentuated trabeculae and 5 showed lysis. On MRI, eight were T1 hyperintense, six were T1 hypointense and all were T2 hyperintense. 11 symptomatic patients underwent treatment: chemical ablation (n = 6), angioembolization (n = 3, 2 had subsequent surgery), radiotherapy (n = 2, 1 primary and 1 adjuvant) and surgery (n = 4). Median follow-up was 20 months. Four of six patients managed only by percutaneous methods had symptom resolution. Three of four patients requiring surgery had symptom resolution.

Conclusion:

Aggressive haemangiomas cause significant morbidity. Treatment is multidisciplinary, with surgery reserved for large lesions and those with focal neurological signs. Minimally invasive procedures may be successful in smaller lesions.

Advances in knowledge:

Aggressive haemangiomas are rare, but knowledge of their imaging features and treatment strategies enhances the radiologist''s role in their management.