Is paracetamol responsible for fatal acute liver failure in pediatric patients after hip dysplasia surgery?

OBJECTIVE: It is well known that local complications, such as avascular necrosis and arthrosis can develop after surgery for developmental dysplasia of the hip (DDH). Thus far, systemic complications that may develop in such cases have not been identified in the literature. This study is the first case series to evaluate acute liver failure (ALF) development after DDH surgery in pediatric patients. PATIENTS AND METHODS: Six patients, five female and one male, who underwent DDH surgery were selected for this study. Perioperative fasting time, laboratory values, treatments, histopathological evaluations, and prognoses after ALF in these patients were evaluated retrospectively. RESULTS: All the patients were administered paracetamol and sevoflurane in therapeutic doses. The patients were referred postoperatively to our pediatric emergency department after 5 ± 1.67 days (range = 3-7 days) on average. The average perioperative fasting time was 9.3 ± 0.82 hours (range = 8-10 hours). Due to the very high aminotransferases and use of paracetamol, intravenous N-acetylcysteine was administered alongside supportive treatments to all the patients. After liver transplantation, two of three patients with grade 3 encephalopathy, died in the early postoperative period. Histopathological evaluations of the three patients' explants were compatible with toxic hepatitis due to paracetamol. CONCLUSIONS: Paracetamol is a commonly used analgesic after pediatric surgery. The therapeutic dose of paracetamol remains uncertain in children who have been fasting for a long time and have been exposed to hepatotoxic drugs due to previous surgery. In conclusion, caution should be exercised in the use of paracetamol in children with DDH who will undergo surgery, and careful perioperative clinical and laboratory monitoring for ALF is essential.

Evaluation of gestational age based on ultrasound fetal growth measurements.

Monitoring fetal growth and assessing its predictors have important place in antenatal care management. Accurate prediction of gestational age (GA) and birth weight (BW) is clinically important. Standard growth curve chosen should be evaluated to see if it satisfies the criteria for a valid assesment. In this paper, for the purpose of contributing to develop national standards and to evaluate Hadlock's standard data pertaining to 1411 fetuses were examined. Of 1411 normally growing fetuses, one measurement for AC, BPD and FL was taken by ultrasound. GA was assessed via menstrual history which is also confirmed by ultrasonography. Several variables, AC, BPD, FL, FL/AC, BPD/FL and dependent variables (GA & BW) were modelled mathematically. Percentile values, correlation coefficients were calculated and well functioning regression equations were produced for the fetal growth evaluation. Simple correlation model re-confirmed that AC, BPD and FL were well predictors of GA. Via modelling by multivariate regression analysis (adj. R2=937), GA=4.945 (95% CI: 4.661- 5.654) + .606 AC + .105 BPD + .286 FL can be estimated. It couldn't be possible establishing an appropriate equation for prediction of BW with current data. Our study is intended to draw an attention on requirement of national standards although Hadlock's standard growth curve may evaluate fetal development accurately. Forming comprehensive cohort group is under our consideration. The equation we developed (shown in the results), might be a working contribution.

Nerve growth factor (NGF) and NGF mRNA change in rat uterus during pregnancy.

During pregnancy, the uterus undergoes a profound sympathetic denervation. To explore whether this is associated with changes in neurotrophic factors, we assayed nerve growth factor (NGF) and NGF mRNA in the uterus of non-pregnant and pregnant rats. In the uterine horn, the concentration of NGF and its mRNA decreased during middle and late pregnancy. However, when values were corrected for the increase of uterine weight and total RNA yield during pregnancy, NGF content and mRNA per horn increased during middle and late pregnancy. Similar, but less pronounced, changes were observed in the cervix. By seven days postpartum, both parameters returned to near normal.

Evaluation of hepatic venous pulsatility and portal venous velocity with Doppler ultrasonography during the puerperium.

OBJECTIVE: The aim of this study is to evaluate pregnancy-induced changes of hepatic venous pulsatility and portal venous velocity in the puerperium and to determine if these changes disappeared by the end of the puerperium. METHODS AND MATERIAL: Healthy normal volunteers (90) were examined on the 2nd and 7th days of puerperium and between the 6th and 8th weeks postpartum. Doppler waveform patterns were obtained in the middle hepatic vein and main portal vein. The hepatic venous pulsatility was named as normal, damped or flat. RESULTS: On the 2nd day postpartum, the hepatic vein pulsatility was shown as normal in 8 (26%), damped in 11 (37%) and flat in 11 (37%) cases. On the 7th day postpartum, 15 (50%) cases had normal, 9 (30%) cases had dampened, and 6 (20%) cases had still flat pattern. The majority of the cases (60%) displayed normal hepatic venous pulsatility in the 6th and 8th weeks of puerperium, whereas 23% had still dampened and 17% had flat patterns. There was a trend toward normal pulsatility with increasing puerperal age. The mean portal venous velocity was still higher than the non-pregnant levels and did not showed significant alterations during puerperium. CONCLUSION: This study emphasised that, since pregnancy-induced alterations in hepatic venous pulsatility and portal venous velocity had not completely returned to normal in most cases until the end of the puerperium, these physiological changes should be considered whenever hepatic and portal systems are interpreted with Doppler sonography during the puerperal period.

The fetal stomach circumference/abdominal circumference ratio: a possible parameter in assessing fetal stomach size.

Nonvisualized, dilated or even a small fetal stomach can be associated with a variety of anomalies and poor fetal outcome. Therefore, we attempted to evaluate the stomach circumference (SC)/abdominal circumference (AC) ratio to assess normal limits of fetal stomach size. A total of 363 fetuses ranging from 15 to 39 weeks' gestation were prospectively evaluated with ultrasonography. The SC was measured from a plane that is perpendicular to the fetal longitudinal axis at the level where the largest axial circumference of the stomach was obtained using a digitizer. The AC was also measured at the same section and the ratio was calculated by dividing the SC by the AC and multiplying by 100. The SC increased linearly from 15 to 24 weeks and showed fluctuations in size thereafter to 39 weeks. A strong correlation was noted between gestational age and both SC (r: 0.842, P < 0.0001) and AC (r: 0.975, P < 0.0001). The SC/AC ratio was normally distributed with a mean of 20.4 +/- 3.9% and ranged between 14.8% and 27.03% throughout pregnancy (r: 0.021, P > 0.05). Although the fetal stomach is a dynamically changing organ, the SC/AC ratio can be considered as a potentially useful parameter in assessing fetal stomach size.

Progesterone profiles in luteal-phase defects associated with recurrent spontaneous abortions.

PURPOSE: Histologically documented luteal-phase defects (LPD) have been detected in 20-40% of women with recurrent spontaneous abortions. In 28 patients with recurrent spontaneous abortions, luteal-phase serum progesterone (P) levels (days 19, 21, 23, 25) and endometrial biopsies were evaluated. METHODS: On the basis of endometrial biopsy findings, the patients were separated into two groups: Group 1, recurrent spontaneous abortions with LPDs (n = 18); and Group 2, recurrent spontaneous abortions with normal biopsies (n = 7). The data are shown in the table below. CONCLUSIONS: This study demonstrated that the P values found in Group 1 were significantly lower than those in Group 2, almost throughout the luteal phase. The results also indicate a close relationship between the P profile in the luteal phase and endometrial biopsy.

The assessment of LH surge for predicting ovulation time using clinical, hormonal, and ultrasonic indices in infertile women with an ensemble of neural networks.

An ensemble of independently trained neural networks (NN) is proposed for the assessment of luteinizing hormone (LH) surge for predicting ovulation time in infertile but ovulating women. The proposed ensemble involves a number of parallel NN modules. Each pair of the NNs learn specific data that are previously collected for monitoring timing function of LH estradiol (pg ml-1), and follicle diameter (mm) are used to train NN pairs to approximate the function of the LH values. A reasonable and accurate estimation places ovulation approximately 10-12 h after the LH peak. The double-valued (bi-phasic) regions of training data are separated into two single-valued (bi-phasic) regions of training data are separated into two single-valued parts (not exactly preovulatory, postovulatory division) that can be learned by each module of the NN pair. During testing, after the initial decision to have single-valued sides, the assessment is obtained by a linear opinion pool (consensus rule) using the decisions of NNs on the corresponding side without waiting. The network ensemble has various desirable properties: high assessment accuracy of a double-valued multisource data, minimized learning and recall times, and a parallel structure. The ovulation time can be predicted through the assessment of LH peak with a better precision and fewer number of tests.

Pharmacological characterization of the muscarinic receptors mediating phosphoinositide hydrolysis in rat myometrium.

Activation of rat uterine myometrial muscarinic receptors with a variety of agonists results in increased phosphatidylinositol metabolism. Activation with carbachol is concentration- and time-dependent and is most apparent by following the accumulation of inositol monophosphate although there are small but significant increases of inositol bisphosphate and inositol trisphosphate. Carbachol stimulation of phospholipid turnover is greatest in the upper third of the uterus. The carbachol-induced increase of inositol monophosphate is antagonized by atropine and by the selective M-3 muscarinic receptor antagonist 4-diphenylacetoxy-N-methylpiperidine methobromide. Pirenzepine, a selective M-1 receptor antagonist is less active, whereas gallamine and 11-2[[(diethylamino)methyl]-1-piperidinyl]acetyl]-5, 11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepine-6-one, selective M-2 receptor antagonists, are minimally effective suggesting that muscarinic M-3 receptors modulate phospholipid turnover in the rat myometrium. Displacement of tritium-quinuclidinyl benzilate binding by muscarinic antagonists also supports the presence of M-3 receptors in the uterus. Incubation with phorbol 12, 13-dibutyrate significantly reduced the accumulation of inositol monophosphate induced by carbachol implying that protein kinase C might modulate the responsiveness of the M-3 receptors in the rat uterus. Our results suggest that the intracellular concentration of calcium required for the contraction of the rat myometrium may be modulated, in part, through M-3 muscarinic receptors coupled to phospholipase C-activated turnover of phosphoinositides.

Angiotensin II stimulates phosphoinositide turnover in the rat myometrium.

Angiotensin II (AII) activates rat myometrium phospholipase C resulting in the hydrolysis of phosphoinositides. The response to AII is concentration- and time-dependent, and it is blocked by saralasin. During pregnancy there is a loss of responsiveness to AII at the site of placental implantation that appears to return during parturition.

Gestational alterations in phospholipase C coupled muscarinic response.

In the pregnant rat, carbachol-induced phosphoinositol hydrolysis by myometrium at the placental attachment region progressively decreased toward term, whereas hydrolysis was relatively stable in the myometrium of the non-attachment region. Tritium-quinuclidinyl benzilate binding increased in the myometrium of non-attachment regions as pregnancy progressed. At placental attachment sites binding remained relatively stable until parturition when it increased. Apparently the myometrium associated with the placental attachment site is less sensitive to cholinergic influence during pregnancy compared with the non-attachment site when evaluated by muscarinic activation of phospholipase C or ligand binding.

Persistent progesterone production associated with autoimmune oophoritis. A case report.

A woman with autoimmune oophoritis was found to have luteal phase progesterone levels throughout a six-month period of amenorrhea. The common presentation of amenorrhea or metrorrhagia, despite the presence of a corpus luteum, in women with autoimmune oophoritis might result from this chronic progesterone production. A clinical picture consistent with a persistent corpus luteum may be a very early sign of autoimmune oophoritis.