Abnormal liver function tests associated with severe rhabdomyolysis

Rhabdomyolysis is a syndrome of skeletal muscle injury with release of cellular constituents such as potassium,phosphate,urate and intracellular proteins such as myoglobin into the circulation,which may cause complications including acute kidney injury,electrolyte disturbance and cardiac instability.Abnormal liver function tests are frequently observed in cases of severe rhabdomyolysis.Typically,there is an increase in serum aminotransferases,namely aspartate aminotransferase and alanine aminotransferase.This raises the question of liver injury and often triggers a pathway of investigation which may lead to a liver biopsy.However,muscle can also be a source of the increased aminotransferase activity.This review discusses the dilemma of finding abnormal liver function tests in the setting of muscle injury and the potential implications of such an association.It delves into some of the clinical and experimental evidence for correlating muscle injury to raised aminotransferases,and discusses pathophysiological mechanisms such as oxidative stress which may cause actual liver injury.Serum aminotransferases lack tissue specificity to allow clinicians to distinguish primary liver injury from muscle injury.This review also explores potential approaches to improve the accuracy of our diagnostic tools,so that excessive or unnecessary liver investigations can be avoided.     

Lung and heart volumes by three-dimensional ultrasound in normal fetuses at 12-32 weeks' gestation.

OBJECTIVE: To establish reference intervals for the fetal right, left and total lung volumes and heart volume between 12 and 32 weeks of gestation. METHODS: Fetal lung and heart volumes were measured using three-dimensional (3D) ultrasound in 650 normal singleton pregnancies at 12-32 weeks. The VOCAL (Virtual Organ Computer-aided AnaLysis) technique was used to obtain a sequence of six sections of each lung and the heart around a fixed axis, each after a 30 degrees rotation from the previous one. The rotation axis for the lungs extended from the apex to the upper limit of the diaphragm dome, and the rotation axis for the heart extended from its apex to its connection to the great vessels. The contour of each of these organs was drawn manually in the six different rotation planes to obtain the 3D volume measurement. In 60 cases the fetal lungs and heart volumes were measured by the same sonographer twice and also by a second sonographer once in order to compare the measurements and calculate intra- and interobserver agreement. RESULTS: The total lung volume and heart volume increased with gestation, from respective mean values of 1.6 and 0.6 mL at 12 weeks to 10.9 and 4.3 mL at 20 weeks and 49.3 and 26.6 mL at 32 weeks. The right to left lung volume ratio did not change significantly with gestation (median, 0.7), whereas the heart to total lung volume ratio increased with gestation from about 0.3 at 12 weeks to 0.5 at 32 weeks. In the Bland-Altman plot, the difference between paired measurements by two sonographers was, in 95% of the cases, less than 0.05, 0.5 and 1.9 mL for each lung at 12-13, 19-22 and 29-32 weeks, respectively, and the corresponding values for the heart volumes were 0.04, 0.4 and 2.3 mL. CONCLUSIONS: In normal fetuses the lung and heart volumes increase between 12 and 32 weeks of gestation. The extent to which in pathological pregnancies possible deviations in these measurements from normal prove to be useful in the prediction of outcome remains to be determined.     

Responses of CDKs and p53 in Delayed Ischemic Neuronal Death

Stroke is a debilitating disease that affects millions each year.While in many cases cerebral ischemic in jury can be limited by effectivw resuscitation or thrombolytic treatment,the injured neurons wither in a process known as delayed neuronal death(DND).Mounting evidence indicates that DND is not simply necrosis played out in slow motion but apoptosis is triggered.Of particular interest are two groups of signal proteins that participate in apoptosis-cyclin dependent kinases(CDKs) and p53-among a myriad of signaling events after an ischemic insult.Recent investigations have shown that CDKs,a family of enzymes initially known for their role in cell cycle regulation,are activated in injured neurons in DND.As for p53,new reports suggest that its up-regulation may represent a failed attempt to rescue in jured neurons,although its up-regulation was previously considered an indication of apoptosis.These observations thus rekindle an old quest to identify new neuroprotective targets to minimize the stroke damage.In this review,the author will examine the evidence that indicates the participation of CDKs and p53 in DND and then introduce pre-clinical data to explore CDK inhibition as a potential neuroprotective target.Finally,using CDK inhibition as an example,this paper will discuss the pertinent criteria for a viable neuroprotective strategy for ischemic in jury.     

Congenital bacterial sepsis in very preterm infants.

The results of body fluid and surface cultures from 148 preterm infants less than 33 weeks gestational age obtained routinely on admission to a neonatal intensive care unit were reviewed. The aim was to determine the occurrence of congenital bacterial sepsis in this population and to examine whether surface cultures yielded information helpful in management. Gastric aspirate and umbilical, nasal and ear swabs were cultured and the results were compared to those of blood cultures. Nine infants (5.4%) had congenital bacterial sepsis diagnosed by positive blood cultures. Only the results of microscopy of gastric aspirate were available within hours of birth and before the results of blood culture. Microscopy of gastric aspirate, demonstrating pus cells, alone had a sensitivity of 0.86 in predicting congenital sepsis but a specificity of 0.49; the specificity, however, rose to 0.80 if both organisms and pus cells were observed on microscopy. Thus, only this combination was a useful pre-indicator of congenital sepsis. In infants who did not develop septicaemia, treatment was modified only if Streptococcus agalactiae was cultured from surface sites; in all such cases, the organism was grown from the ear swab. Our results demonstrate that congenital bacterial sepsis is common amongst very preterm infants admitted for neonatal intensive care but routine screening of surface cultures should be restricted to an ear swab only.     

Second-trimester sex hormone-binding globulin and subsequent development of pre-eclampsia.

OBJECTIVE: To investigate whether maternal plasma sex hormone-binding globulin (SHBG) concentrations are reduced in women who subsequently develop pre-eclampsia. METHODS: This was a cross-sectional study, carried out at antenatal clinics in seven hospitals in and around London. Healthy women underwent uterine artery Doppler velocimetry as a screening method for pre-eclampsia at 22-24 weeks of gestation. The first group (408 women) had normal uterine artery Doppler waveforms (mean uterine artery pulsatility index (PI) below 1.6). The second group (274 women) had increased impedance to flow in the uterine arteries (mean PI above the 95th centile, 1.6). Maternal plasma SHBG concentrations were measured retrospectively using a competitive chemiluminescent immunoassay. Pre-eclampsia was as defined by the International Society for the Study of Hypertension in Pregnancy. RESULTS: Plasma SHBG concentrations in the 80 (11.7%) women who subsequently developed pre-eclampsia were significantly lower than in the 585 (85.8%) women with normal pregnancy outcomes (median 336, range 142-674 nmol/l vs. median 336, range 142-674 nmol/l, p = 0.001). There was a strong correlation between SHBG concentrations and body mass index (r =-0.232246, p < 0.0001). There were no significant differences in maternal plasma SHBG concentrations in women with abnormal uterine artery Doppler (n = 274) compared with controls (n = 408) (median 324, range 101-635 nmol/l vs. median 336, range 142-674 nmol/l, p = 0.09). CONCLUSION: Maternal plasma SHBG concentrations are reduced in women who subsequently develop pre-eclampsia.     

Predicting the severity of fetal anemia using time-domain measurement of volume flow in the fetal aorta.

OBJECTIVES: To assess the value of fetal aortic time-domain measurement of volume flow (using color velocity imaging quantification (CVI-Q)) in predicting the severity of fetal anemia. METHODS: This was a prospective observational study, in which 24 pregnant women with suspected fetal anemia due to rising anti-red blood cell antibody titers underwent cordocentesis. The fetal aortic time-domain volume flow was measured before fetal blood sampling for fetal hemoglobin investigation. We examined the correlation between increased fetal aortic time-domain volume flow (>2 SD for gestational age) and fetal anemia (hemoglobin level <2 SD for gestational age). RESULTS: Seventeen fetuses had anemia, and seven had normal hemoglobin. There was a strong correlation between the increase in fetal aortic time-domain volume flow and the drop in hemoglobin value (r = 0.81; P < 0.01). The sensitivity of this technique to predict fetal anemia was 81.3% and the specificity was 71.4%. The mean increase over time in aortic CVI-Q in anemic fetuses was 323.2 mL/min (95% CI, 200.1 to 446.4) compared with 86.9 mL/min (95% CI, -17.7 to 191.5) in the non-anemic group (P = 0.004). CONCLUSION: Fetal aortic time-domain measurement of volume flow is significantly increased in cases of fetal anemia due to red-cell alloimmunization. These findings can be used to improve the sensitivity, specificity and positive predictive value of the non-invasive techniques used to predict fetal anemia, and may help in the selection of pregnancies that require cordocentesis and transfusion.     

Evaluation of the effects of elastic compression in patients with postphlebitic limbs by laser-Doppler flowmetry

Laser-Doppler flowmetry has been used to study the skin microcirculation in 20 normal limbs and 80 limbs of patients with venous hypertension and leg ulceration due to deep venous reflux. It was found that limbs with venous hypertension had a high skin resting blood flow (BRF) and an impaired veno-arteriolar reflex (VR). There was a marked improvement in both BRF and VR after elastic compression for three weeks and an association between this improvement and the rate of healing of the leg ulcers. The results indicate that elastic compression may affect the microcirculation even though it does not alter the venous pressure measurements when the elastic stockings are removed.     

Femorodistal vein bypass graft stenoses

Eighty femorodistal in situ vein bypass grafts have been evaluated at 3-monthly intervals clinically, with ankle:brachial pressure indices (ABI), by intravenous digital subtraction angiography (IV DSA) and by Duplex scanning. Five grafts (6 per cent) failed in the perioperative period. Nineteen (25 per cent) of the remaining 75 grafts subsequently developed stenoses on IV DSA during the first 12 months. All angiographic stenoses were detected by Duplex scanning using velocity ratio criteria before the development of symptoms or a measurable decline in ABI, i.e. while non-haemodynamically significant. This technique involves scanning the entire length of the graft but allows even minor stenoses to be detected and progression of stenoses can be determined. At a mean follow-up of 12 months (3-18 months), four (7 per cent) of the fifty-six grafts without stenoses occluded. Eight (42 per cent) of the nineteen stenosed grafts either occluded or developed symptoms. None of the occluded grafts in this series could be salvaged. Non-haemodynamically significant vein stenoses can be detected non-invasively, occur frequently and are associated with graft failure.