An experience of ultrasound-guided hydrostatic reduction of intrussusception at a tertiary care centre.

BACKGROUND: Intussusception is an important and one of the most commonly encountered diagnoses of intestinal obstruction in the paediatric age group. Ultrasound-guided hydrostatic reduction is an effective, nonoperative treatment modality for this condition and is associated with a high success rate. In addition, it is simple and safe as the entire procedure is carried out with real-time ultrasound, without the hazard of radiation. The aim of this study was to evaluate the effi cacy and safety of ultrasound-guided hydrostatic reduction in the management of intussusceptions in the paediatric age group. METHOD: A case study was carried out on 89 patients diagnosed with intussusception using high-resolution ultrasonography over a period of two years, spanning February 2012 to January 2014. Ultrasound-guided hydrostatic reduction was performed in 78 of these patients, and 11 patients were excluded owing to clinical contraindications. Follow-up ultrasound was performed after 24 hours to rule out recurrence. RESULTS: The disease was most prevalent in the age group 6-24 months. The ileocolic type was the most common. Mean duration (hours) was 17.02 ± 20.81 for time to presentation. Complete therapeutic reduction was achieved in 70 of the 78 cases, with a success rate of 90%. Two recurrences occurred in the following 24 hours, which were successfully reduced on the second attempt. Complications and mortality did not occur secondary to the procedure. CONCLUSION: Our study found that ultrasound-guided hydrostatic reduction is a simple, safe and effective nonoperative treatment for intussusceptions in the paediatric age group, and should be the fi rst line of management in appropriate patients.

Redox phospholipidomics of enzymatically generated oxygenated phospholipids as specific signals of programmed cell death.

High fidelity and effective adaptive changes of the cell and tissue metabolism to changing environments require strict coordination of numerous biological processes. Multicellular organisms developed sophisticated signaling systems of monitoring and responding to these different contexts. Among these systems, oxygenated lipids play a significant role realized via a variety of re-programming mechanisms. Some of them are enacted as a part of pro-survival pathways that eliminate harmful or unnecessary molecules or organelles by a variety of degradation/hydrolytic reactions or specialized autophageal processes. When these "partial" intracellular measures are insufficient, the programs of cells death are triggered with the aim to remove irreparably damaged members of the multicellular community. These regulated cell death mechanisms are believed to heavily rely on signaling by a highly diversified group of molecules, oxygenated phospholipids (PLox). Out of thousands of detectable individual PLox species, redox phospholipidomics deciphered several specific molecules that seem to be diagnostic of specialized death programs. Oxygenated cardiolipins (CLs) and phosphatidylethanolamines (PEs) have been identified as predictive biomarkers of apoptosis and ferroptosis, respectively. This has led to decoding of the enzymatic mechanisms of their formation involving mitochondrial oxidation of CLs by cytochrome c and endoplasmic reticulum-associated oxidation of PE by lipoxygenases. Understanding of the specific biochemical radical-mediated mechanisms of these oxidative reactions opens new avenues for the design and search of highly specific regulators of cell death programs. This review emphasizes the usefulness of such selective lipid peroxidation mechanisms in contrast to the concept of random poorly controlled free radical reactions as instruments of non-specific damage of cells and their membranes. Detailed analysis of two specific examples of phospholipid oxidative signaling in apoptosis and ferroptosis along with their molecular mechanisms and roles in reprogramming has been presented.

NDPK-D (NM23-H4)-mediated externalization of cardiolipin enables elimination of depolarized mitochondria by mitophagy.

Mitophagy is critical for cell homeostasis. Externalization of the inner mitochondrial membrane phospholipid, cardiolipin (CL), to the surface of the outer mitochondrial membrane (OMM) was identified as a mitophageal signal recognized by the microtubule-associated protein 1 light chain 3. However, the CL-translocating machinery remains unknown. Here we demonstrate that a hexameric intermembrane space protein, NDPK-D (or NM23-H4), binds CL and facilitates its redistribution to the OMM. We found that mitophagy induced by a protonophoric uncoupler, carbonyl cyanide m-chlorophenylhydrazone (CCCP), caused externalization of CL to the surface of mitochondria in murine lung epithelial MLE-12 cells and human cervical adenocarcinoma HeLa cells. RNAi knockdown of endogenous NDPK-D decreased CCCP-induced CL externalization and mitochondrial degradation. A R90D NDPK-D mutant that does not bind CL was inactive in promoting mitophagy. Similarly, rotenone and 6-hydroxydopamine triggered mitophagy in SH-SY5Y cells was also suppressed by knocking down of NDPK-D. In situ proximity ligation assay (PLA) showed that mitophagy-inducing CL-transfer activity of NDPK-D is closely associated with the dynamin-like GTPase OPA1, implicating fission-fusion dynamics in mitophagy regulation.

Maternal serum markers levels in consecutive pregnancies: a possible genetic predisposition to abnormal levels.

The study comprised 2,361 women, each with two consecutive normal uncomplicated pregnancies screened at 15-20 weeks gestation for maternal serum alpha-fetoprotein levels (AFP). In 1,816 of these women, maternal serum human chorionic gonadotropin (hCG) levels were tested as well. The proportion of women who had a second high AFP level (> or = 2.0 MOM) in their subsequent pregnancy was 6.5-fold higher as compared with the proportion of women who had normal levels of AFP in their first tested pregnancy. The relative chance of having a second positive result of a low level of AFP (AFP < or = 0.5 MOM) in subsequent pregnancies was 3.8-fold higher. The relative chances of having a second positive result of high or low levels of hCG were 3.9- and 2.2-fold higher, respectively. It is concluded that there is a predisposition for abnormal levels of serum markers that is influenced by genetic and/or environmental factors. Therefore it is suggested that the individual's risk of having a Down syndrome baby, or other adverse pregnancy outcome that is derived from the serum markers' levels, should be adjusted taking into account unexplained high or low levels in previous pregnancies. A screening policy is suggested which is designed to yield a lower false-positive rate without affecting the detection rate of abnormal pregnancies. More data are needed before an accurate adjustment based on previous results can be made.

New heritable fragile site with spontaneous expression at 1q41.

The report presents a family ascertained through recurrent spontaneous abortions in which a new heritable fragile site located at 1q41 is segregating. The fragile site is present in the mother and her son. It is expressed spontaneously in 100% of the metaphases from lymphocyte culture using standard conditions. The use of folate deficient medium and the addition of FUdR to the medium did not affect the appearance nor the level of expression of the fragile site.

Paracentric inversion of Xq and ovarian dysfunction.

We report on a paracentric inversion X(q13 q24) in a 20-year-old woman with ovarian dysfunction. The findings add evidence on the role of breakpoints in Xq13 and Xq24 in causing ovarian dysfunction. A review of the published data on paracentric inversion of chromosome X is included.

New multiple congenital anomalies: mental retardation syndrome (MCA/MR) with facio-cutaneous-skeletal involvement.

Five unrelated patients (a male and 4 females) were affected with a previously undefined multiple congenital anomalies/mental retardation syndrome which has been designated the facio-cutaneous-skeletal (FCS) syndrome and which includes mental retardation with specific sociable, humorous behavior, characteristic facial appearance, excessive generalized skin, postnatal growth failure, and skeletal involvement. Consanguinity was noted in 2 patients, thus autosomal recessive inheritance is suggested.

Deletion of the short arm of chromosome 10 (10p13): report of a patient and review.

Since the first description by Elliot et al. [1970, Am J Dis Child 119:72-73] of a probable partial deletion of chromosome 10p, 17 other cases have been reported. The phenotypic expression is variable, but the craniofacial malformations constitute a more consistent finding. The 10p deletion syndrome has been associated with the DiGeorge anomaly in several patients. We report on an additional case of 10p deletion syndrome and review the literature.

Neu-Laxova syndrome: prenatal ultrasonographic diagnosis, clinical and pathological studies, and new manifestations.

A diagnosis of the Neu-Laxova syndrome (NLS) was made by ultrasonography at 32 wks of gestation. Ultrasonographic examination showed intrauterine growth retardation (IUGR), Dandy-Walker anomaly, choroid plexus cysts, receding forehead and microcephaly, bilateral cataract without prominent eyes, scalp edema with no generalized edema, retrognathia, curved penis, and flexion deformities of limbs. The findings in this case are consistent with NLS; however, they did not fit any of Curry's [1982] groups. Massive swelling of hands and feet were among the main manifestations in classic NLS cases. In the case presented herein, edema was noted only in the scalp. This might shed further light on the question of variability vs. heterogeneity in the NLS. This case shows the existing possibility of an early diagnosis of NLS and adds Dandy-Walker anomaly and choroid plexus cysts as new findings to this syndrome.

Interstitial deletion (6)q13q15.

We report on a 2-year-old child with psychomotor retardation, facial and urogenital anomalies. His chromosome constitution was 46,XY, del(6)(q13q15). This case further contributes to the karyotype-phenotype correlation of proximal deletion 6q syndromes.

Inherited inverted duplication of X chromosome in a male: report of a patient and review of the literature.

Nineteen cases of duplication of segments of the long arm of chromosome X have been published in 13 males and in 6 females. We report an additional case of a male with growth and mental retardation, growth hormone deficiency, compensated primary hypothyroidism, distinctive anomalies of the face, hypoplastic genitalia, and hypotonia in whom inverted duplication of a segment in the long arm of X chromosome was diagnosed, 46,Y, dup (X)(q21.2q13.3), and mosaicism was demonstrated in his mother's X chromosome. The rearranged segment was diagnosed utilizing high resolution G-band technique and FISH studies, using chromosome X total chromosome probe and DNA XIST probe. This appears to be the first report of a patient with duplication of Xq and hypothyroidism.

The association between unexplained second-trimester maternal serum hCG elevation and pregnancy complications.

OBJECTIVE: We conducted this cohort analytic study to determine whether women with unexplained elevations of maternal serum hCG at 16-20 weeks' gestation are at increased risk for pregnancy complications and adverse perinatal outcomes. METHODS: The inclusion criteria were a singleton gestation, a confirmed gestational age, and an hCG level greater than 2.5 multiples of the median (MOM). The exclusion criteria were fetal anomalies, an abnormal karyotype, and a maternal serum alpha-fetoprotein (MSAFP) level greater than 2.5 MOM. A group of randomly selected women with normal hCG and MSAFP levels served as controls. RESULTS: Of the 6011 women screened, 284 (4.7%) had an unexplained elevated hCG level. Patients with elevated levels of hCG had a significantly higher risk for hypertension (odds ratio 4.4; 95% confidence interval [CI] 1.9-10) and fetal growth restriction (odds ratio 2.8; 95% CI 1-7). Women with hCG levels greater than 4 MOM also had an increased risk of preterm delivery (odds ratio 3.3; 95% CI 1.3-8.2). CONCLUSION: Pregnancies with unexplained elevated hCG levels should be regarded as high-risk pregnancies and managed accordingly.

Alpha-fetoprotein in the early neonatal period--a large study and review of the literature.

BACKGROUND: Alpha-fetoprotein (AFP) is a glycoprotein molecule, which has similarity to albumin and is produced by the fetal liver. Its biological role is unclear and factors that may influence its concentrations in neonates are only partially identified. However, it has an important role as a diagnostic marker, especially in certain tumors and liver diseases of childhood. Its normal reference values in newborns have not been well defined. METHODS: Serum AFP concentrations were measured and characterized in 260 term and near-term newborns [gestational age (GA)> or =34 weeks, birthweight (BW)> or =1700 g] at birth [umbilical cord (UC) blood] and upon discharge from the nursery at 60+/-24 h of life (venous sample). RESULTS: Due to the nonnormal distribution of AFP levels, it is useful to relate to reference interval for AFP concentrations at birth that was 15.7-146.5 microg/ml, based on 95% confidence interval (CI). The median value of 48.3 microg/ml is also a useful reference. However, mean AFP concentrations at birth that were 61.6+/-44.8 microg/ml are less informative due to the large standard deviation (S.D.). Upon discharge, AFP concentrations dropped to 9.7-111.9 microg/ml (95% CI) with a median of 34.2 microg/ml. A significant negative correlation was found between AFP serum levels and gestational age and to a lesser extent with birthweight. No significant differences were found between males and females. CONCLUSIONS: Normal reference intervals for AFP in term and near-term newborns have been defined, but need to be addressed with caution due to the wide range of normal values. AFP levels at birth decrease as gestation advances and the newborn weighs more.

The karyotype of fetuses with anomalies detected by second trimester ultrasonography.

OBJECTIVE: To determine the incidence of abnormal karyotype among fetuses with anomalies detected by detailed second trimester ultrasonography. STUDY DESIGN: A total of 573 patients underwent amniocentesis following the detection of anomalies by detailed second trimester ultrasonography. RESULTS: Thirty-six (6.3%) fetuses with abnormal karyotype were detected. The most common abnormal karyotypes were: trisomy 18, 11 cases; trisomy 21, 8 cases; 45XO, 7 cases; trisomy 13, 3 cases; and triploidy, 2 cases. Abnormal karyotype was detected in 20/111 (18%) fetuses with more than one anomaly, 15/182 (8.2%) with cystic hygroma, and 1/38 with nuchal thickening. No abnormal karyotype was detected among 108 fetuses with choroid plexus cyst, 58 with hydronephrosis, 25 with ventriculomegaly, 16 with a single umbilical artery, 18 with cardiac anomalies. CONCLUSIONS: (1) Half of the cases with abnormal karyotype occurred in fetuses with more than one anomaly. (2) Cystic hygroma was the isolated malformations most commonly associated with abnormal karyotype. (3) Isolated malformations such as choroid plexus cyst or hydronephrosis were not associated with abnormal karyotype.

46,XX gonadal dysgenesis associated with congenital nerve deafness.

A sporadic case of a woman presenting with the combination of pure 46,XX gonadal dysgenesis and congenital nerve deafness is reported. A similar association had been reported as a rare familial occurrence. The apparent heterogeneity of phenotypic characteristics among the previously reported individuals and the possible genetic implications are discussed.

Autosomal translocation in an apparently normospermic male as a cause of habitual abortion.

A 22;22 Robertsonian translocation was diagnosed in a husband whose wife had had six consecutive early spontaneous abortions and no normal progeny. With the new multiple-exposure photography (MEP) technique, an accurate, objective and documentary sperm analysis was performed. No abnormality of the essentially defective, genetically unbalanced sperms could be detected in regard to sperm count, motility, velocity and morphology. The only similar translocation previously reported in a male was associated with azoospermia. Recent literature correlating chromosomal aberrations and reproductive failure in the male is discussed in relation to the reported case. The importance of including the male partner in the cytogenetic investigation of couples with habitual abortion is stressed.

[Non-cardiac pulmonary edema: an enigma today]. / Edema polmonare non cardiaco: enigma di attualità.

Pulmonary oedema is caused by an excessive accumulation of interstitial fluid in the lungs: in the case of left ventricular failure, oedema arises due to an increase in capillary hydrostatic pressure. Non-cardiac oedema, on the other hand, is brought about by a change in alveolar capillary membrane permeability. Although the causes are different, namely respiratory distress syndrome in adults, altitude-induced pulmonary oedema, oxygen toxicity, medication, metabolic changes, etc., the result is the same, i.e. damage to the alveolar capillary membrane. This damage appears to be brought about by two factors: complement activation and damage to the blood clotting mechanism. The difference between cardiac and non-cardiac pulmonary oedema is difficult to gauge. If pulmonary cone pressure is normal or low, and if the oedematous fluid/plasma protein ratio is greater than 0.7, the oedema is non-cardiac in origin. Treatment is carried out with the aim of repairing the alveolar capillary membrane and preventing extension of the damage. Respiratory insufficiency is treated by a mechanical respirator, applying positive pressure at the end of expiration. Fluid administration is adjusted according to pulmonary cone pressure levels. Opinions are still divided over whether to administer crystalline or colloidal solutions, steroids or protease inhibitors.

[Fanconi anemia syndrome as a predisposing factor for acquired bone marrow aplasia].

A 4-year old girl who received prophylactic therapy with oral cephalexin for 1 year because of a history of urinary tract infections, was referred for evaluation of short stature. On physical examination mildly dysmorphic features were observed. Blood counts disclosed pancytopenia, and bone marrow examination showed hypoplasia of all 3 cell lines. Chromosome analysis after exposure to a DNA cross-linking agent (diepoxybutane) showed a chromosomal breakage pattern consistent with Fanconi anemia. Discontinuation of cephalexin was followed by improvement in hematological values. This course of events supports the hypothesis that acquired bone marrow depression may be a manifestation of Fanconi anemia, warranting the appropriate diagnostic work up in every case of acquired bone marrow aplasia.

[Inborn errors of metabolism: lessons from a clinical case].

Dramatic advances in recent years in the diagnosis and treatment of inborn errors of metabolism (IEM) make it imperative for the physician to be both aware of their occurrence and acquainted with their clinical presentations. Many may present with symptoms and signs common to sick infants, such as refusal to feed, vomiting and convulsions. Failure to include IEM in the differential diagnosis may have grave consequences, because only prompt recognition and appropriate treatment of a metabolic crisis can help prevent irreversible brain damage or death. We describe a 3-week-old female infant, eventually diagnosed as having an IEM (3-hydroxy-3-methyl-glutaric aciduria), who was admitted to various hospitals and died during her last admission. We focused on the clinical and laboratory findings of each of the first 2 admissions which might have provided clues to the true nature of the illness had the clinicians been aware of the possibility of IEM. Patients with IEM are generally managed in specialized centers; however, the responsibility for initial recognition and immediate treatment of a metabolic emergency lies with the primary physician. The purpose of our case presentation and the discussion of the lessons derived from it, is to prompt the clinician to an awareness and understanding of a subject that used to be considered reserved for specialists. In fact, all that is needed is clinical alertness and the performance of certain well-focused, simple laboratory tests for IEM.