Detection and quantitation of constriction of the fetal ductus arteriosus by Doppler echocardiography

Pulmonary hypertension may occur in the fetus in the presence of constriction of the ductus arteriosus. The feasibility of detection and quantitation of fetal ductal constriction by Doppler echocardiography was assessed in an animal preparation in which ductal constriction was created in the fetal lamb with a variable ligature causing varying degrees of fetal pulmonary hypertension (fetal pulmonary arterial systolic pressure 57 to 97 mm Hg and ductal gradient 9 to 42 mm Hg). Comparison of blinded, continuous-wave peak Doppler velocity (V) measurements of the ductal gradient with the modified Bernoulli assumption (gradient = 4V2) compared well with direct catheter measurements of instantaneous peak systolic gradient (r = .99, catheter = 0.95 X Doppler + 0.6), peak-to-peak gradient (r = .97), and mid-diastolic gradient (r = .85). Ductal constriction was characterized by an increase in the peak systolic and diastolic velocities. The normal human fetal ductus arteriosus blood flow velocity pattern was assessed by pulsed Doppler techniques in 25 normal human fetuses after 20 weeks gestation. The peak systolic flow velocity in the ductus arteriosus measured by image-directed pulsed Doppler echocardiography ranged from 50 to 141 cm/sec (mean 80 cm/sec) and increased with gestational age (r = .50). Diastolic velocity in the ductus arteriosus was consistently directed toward the descending aorta and ranged from 6 to 30 cm/sec. The ductal systolic velocities were the highest blood flow velocities in the fetal cardiovascular system. Application of these techniques to fetuses whose mothers were receiving indomethacin for treatment of premature labor at 30 to 31 weeks gestation confirmed this method to be sensitive for detection of fetal ductal constriction, which developed in three fetuses.(ABSTRACT TRUNCATED AT 250 WORDS)     

The Impella Microaxial Flow Catheter Is Safe and Effective for Treatment of Myocarditis Complicated by Cardiogenic Shock: An Analysis From the Global cVAD Registry

Background

Myocarditis complicated by cardiogenic shock remains a complex problem. The use of acute mechanical circulatory support devices for cardiogenic shock is growing. We explored the utility of Impella transvalvular microaxial flow catheters in the setting of myocarditis with cardiogenic shock.

A randomized controlled trial comparing haemodynamic stability in elderly patients undergoing spinal anaesthesia at L5, S1 versus spinal anaesthesia at L3, 4 at a tertiary African hospital

Background

Spinal anaesthesia is a routinely used anaesthetic technique in elderly patients (> 60 years) undergoing operations involving the lower limbs, lower abdomen, pelvis and the perineum. Spinal anaesthesia has several advantages over general anaesthesia including stable haemodynamic variables, less blood loss, less post-operative pain, faster recovery time and less post-operative confusion. Despite these advantages, the sympathetic blockade induced by spinal anaesthesia can result in hypotension, bradycardia, dysrhythmias and cardiac arrests. Conventionally, spinal anaesthesia is performed at the level of L3,4 interspace; with a reported incidence of hypotension in the elderly ranging between 65% and 69%. A possible strategy for reducing spinal induced hypotension would be to minimize the peak block height to as low as possible for the planned procedure.

Objective

To determine the difference in haemodynamic stability between elderly patients undergoing spinal anaesthesia at L5, S1 interspace compared to those at L3, 4.

Methods

Thirty two elderly patients scheduled for lower limb or pelvic surgery under spinal anaesthesia were randomized into 2 groups (control group and intervention group) using a computer generated table of numbers.Control group; received 2.5 mls 0.5% hyperbaric bupivacaine injected intrathecally at the L3, 4 interspace and Intervention group; 2.5mls 0.5% hyperbaric bupivacaine injected intrathecally at the L5, S1 interspace

Results

The two groups had similar baseline characteristics in age, sex, body mass index and use of anti-hypertensive medications. There was 68.8% proportion of hypotension in the control group and 75% in the intervention group. The difference was not found to be statistically significant (p= 0.694). During the study period, there were 106 episodes of hypotension, out of which, 65 were in the control group and 41 in the intervention group (p=0.004).. Linear regression analysis of the decrease in mean arterial pressures (MAP) showed a higher decrease in MAP in the control group (p 0.018). There were more crystalloids used in the control group (1006mls ± 374) than in the intervention group (606mls ±211) with a p< 0.0001. There was no difference in the amounts of vasopressors used between the two groups (p=0.288). There was no difference in the change in heart rates, conversion to general anaesthesia, use of supplementary intravenous fentanyl and the peak maximum block level achieved. The time to peak maximum sensory block level was 9.06min and 13.07min in the control group and intervention groups, respectively (p<0.0001).

Conclusion

Among this population, there was no difference in the proportion of those with hypotension between the elderly patients who received their spinal anaesthesia at L3,4 and those who received spinal anaesthesia at L5,S1. The intervention group had better outcomes with significantly less episodes of hypotension. It took a longer time to achieve a maximum peak sensory block in the intervention group. Performing spinal anaesthesia at the level of L5,S1 was found to provide an adequate sensory block for a wide range of pelvic, perineal and lower limb surgeries.     

Lateral ventricle injection of orexin-A ameliorates central precocious puberty in rat via inhibiting the expression of MEG3

Background: Central precocious puberty (CPP) is characterized as increasing gonadotropin-releasing hormone (GnRH) release. Orexin-A has also been shown to affect GnRH release. However, there are few reports about the effect of orexin A on the treatment of CPP. Methods: After establishing the precocious puberty model, the rats were divided into four groups: normal control, precocious puberty rats, precocious puberty rats treated with normal saline and precocious puberty rats treated with orexin-A. The vaginal opening time, second estrus cycle, ovarian index and uterus index of rats in each group were detected. qRT-PCR was performed to examine the expression of MEG3 and kisspeptin in rats. HT22 cells were transfected with pcDNA-MEG3 to detect the expression of Kisspeptin. Results: In this study, we found that orexin-A not only delayed the day of vaginal opening and regular estrus cycle days but also decreased the ovarian index and uterus index in rats with CPP. In addition, orexin-A reversed the up-regulation of MEG3 and kisspeptin in rats with CPP. In HT22 cells, the mRNA and protein level of kisspeptin were enhanced by pcDNA-MEG3. Conclusion: Our results suggest that orexin-A ameliorates central precocious puberty in rat and MEG3 might be involved in this effect, suggesting that MEG3 might be a novel target in treating central precocious puberty.     

Development trends for generation of single-chain antibody fragments

Recombinant antibodies are increasingly being employed as therapeutic agents especially in combination with anti-cancer drugs. The single-chain antibody fragments are small antigen-binding proteins which provide the most commonly used antibody formats for diagnostic and therapeutic purposes. These antibody fragments have more rapid tumor penetration and clearance from the serum relative to full-length monoclonal antibodies. There are in vitro antibody-display technologies such as phage display, cell surface display, ribosome display and mRNA display that can be used to isolate high specificity and affinity single-chain antibodies against a wide variety of targets. We review these strategies for generation of stable and active antibody fragments in the present article.     

Intermittent fasting during Ramadan: does it affect sleep?

Islamic intermittent fasting is distinct from regular voluntary or experimental fasting. We hypothesised that if a regimen of a fixed sleep–wake schedule and a fixed caloric intake is followed during intermittent fasting, the effects of fasting on sleep architecture and daytime sleepiness will be minimal. Therefore, we designed this study to objectively assess the effects of Islamic intermittent fasting on sleep architecture and daytime sleepiness. Eight healthy volunteers reported to the Sleep Disorders Centre on five occasions for polysomnography and multiple sleep latency tests: (1) during adaptation; (2) 3 weeks before Ramadan, after having performed Islamic fasting for 1 week (baseline fasting); (3) 1 week before Ramadan (non‐fasting baseline); (4) 2 weeks into Ramadan (Ramadan); and (5) 2 weeks after Ramadan (non‐fasting; Recovery). Daytime sleepiness was assessed using the Epworth Sleepiness Scale and the multiple sleep latency test. The participants had a mean age of 26.6 ± 4.9 years, a body mass index of 23.7 ± 3.5 kg m^?2 and an Epworth Sleepiness Scale score of 7.3 ± 2.7. There was no change in weight or the Epworth Sleepiness Scale in the four study periods. The rapid eye movement sleep percentage was significantly lower during fasting. There was no difference in sleep latency, non‐rapid eye movement sleep percentage, arousal index and sleep efficiency. The multiple sleep latency test analysis revealed no difference in the sleep latency between the ‘non‐fasting baseline’, ‘baseline fasting’, ‘Ramadan’ and ‘Recovery’ time points. Under conditions of a fixed sleep–wake schedule and a fixed caloric intake, Islamic intermittent fasting results in decreased rapid eye movement sleep with no impact on other sleep stages, the arousal index or daytime sleepiness.     

Acute promyelocytic leukaemia is characterized by stable incidence and improved survival that is restricted to patients managed in leukaemia referral centres: a pan‐Canadian epidemiological study

Timely diagnosis and care are major determinants of the outcome in acute promyelocytic leukaemia (APL), a malignancy whose incidence may be increasing. The Canadian Cancer Registry (CCR) and health system represent valuable settings to study APL epidemiology. We analysed the CCR, which contains data on all Canadians with APL. To provide clinical information lacking in the CCR, we obtained data from five leukaemia referral centres during a similar time period. Between 1993 and 2007, there were 399 APL in Canada. Age‐standardized incidence was 0·083/100 000 and was stable over time. The early death (ED) rate was 21·8% (10·6% in patients <50 years old and 35·5% for those aged >50 years), with no improvement over time. Five‐year overall survival (OS) was 54·6% (73·3% in patients <50 years; 29·1% older patients). In the referral cohort, 131 patients were diagnosed between 1999 and 2010. ED was 14·6% and 2‐year OS was 76·5%. Within this cohort, ED and OS improved over time, although advanced patient age remained an adverse determinant of OS. In Canada, APL incidence is unexpectedly low and temporally stable. ED was higher than reported in clinical trials, but similar to reports from other registries. In contrast, ED was lower in referral centres and improved with time.