Benefits of a standardised feeding regimen during a clinical trial in preterm neonates.

The feeding regimen was standardised for a trial of erythromycin to reduce the time to reach full feeds (150 ml/kg/day) by 30% in neonates of < or = 32 weeks gestation. No significant improvement was noted in the primary outcome (median time: erythromycin 93.5 vs placebo 104 hours, p = 0.60). However, necrotising enterocolitis > or = stage II disappeared and the time to full feeds was reduced by over 50% in all neonates during the 18-month trial, and for more than two years after the trial, when the standardised feeding regimen was adopted as routine policy for feeding neonates of < or = 32 weeks (< 28 weeks: 13 vs 4.8 days, p < 0.05; > 28 weeks: 8 vs 3.9 days, p < 0.05). This was in contrast to an average of six cases of NEC per year with 45% mortality during the previous five years. The benefits of standardised feeding schedules--improved detection/treatment of signs/symptoms of feed intolerance--are emphasised.

Can prophylactic oral erythromycin reduce time to full enteral feeds in preterm neonates?

Efficacy of oral, prophylactic erythromycin in reducing the time to establish full enteral feeds (150 ml/kg/day) was assessed in neonates < 32 weeks, ready for enteral feeds. Seventy-three consecutive neonates were randomised to receive oral erythromycin ethyl succinate (n = 36) or placebo (n = 37) in a double-blind trial until full enteral feeds or 14 days of therapy were reached. A prospectively designed feeding regimen, including plan of action for signs of feed intolerance, was common for all enrolled neonates. The median gestational age, birth weight and postnatal age at start of feeds were 29 versus 30 weeks (p = 0.40), 1232 versus 1280 g (p = 0.96) and 5 versus 5 days (p = 0.84) for erythromycin and placebo group, respectively. Time to achieve full feeds was not significantly different in the two groups. (median times: erythromycin 93.5 versus placebo 104 hours, p = 0.60). Erythromycin-related side-effects did not occur.

Gestational magnesium deficiency is deleterious to fetal outcome.

A number of recent epidemiological findings have implicated magnesium as being essential to fetal well-being. Few studies, however, have examined the relationship between maternal requirements for dietary magnesium and subsequent mortality and morbidity in offspring. The present study uses a rodent model of dietary-induced hypomagnesemia to investigate the effects of magnesium deficiency prior to and during gestation on neonatal morbidity and mortality. Magnesium deficiency during gestation significantly increased neonatal mortality and morbidity. Such increases were associated with a reduced free magnesium concentration in both maternal and offspring blood and an increased incidence of periventricular hemorrhage and edema in newborn pups as observed by magnetic resonance imaging and histology. Animals fed a magnesium-deficient diet before mating but given magnesium supplementation during gestation did not demonstrate a significant change in neonatal mortality and morbidity when compared to control animals. The significant improvement in fetal outcome with dietary magnesium supports the concept of magnesium supplementation during pregnancy.

A catalytic antibody against cocaine prevents cocaine's reinforcing and toxic effects in rats.

Cocaine addiction and overdose have long defied specific treatment. To provide a new approach, the high-activity catalytic antibody mAb 15A10 was elicited using a transition-state analog for the hydrolysis of cocaine to nontoxic, nonaddictive products. In a model of cocaine overdose, mAb 15A10 protected rats from cocaine-induced seizures and sudden death in a dose-dependent fashion; a noncatalytic anticocaine antibody did not reduce toxicity. Consistent with accelerated catalysis, the hydrolysis product ecgonine methyl ester was increased >10-fold in plasma of rats receiving mAb 15A10 and lethal amounts of cocaine. In a model of cocaine addiction, mAb 15A10 blocked completely the reinforcing effect of cocaine in rats. mAb 15A10 blocked cocaine specifically and did not affect behavior maintained by milk or by the dopamine reuptake inhibitor bupropion. This artificial cocaine esterase is a rationally designed cocaine antagonist and a catalytic antibody with potential for medicinal use.

Meconium thorax: a case report and review of literature.

A case is presented in which extension of meconium peritonitis through muscular defects in the diaphragm lead to intrathoracic calcifications diagnosed sonographically at 23 weeks of gestation. There were three diaphragmatic defects, two small ones corresponded to foramina of Morgagni and one large posterior defect that did not correspond to the foramen of Bochdelak. There were three additional muscular defects: one in the rectus abdominus and two, bilaterally, in the loins. Despite long-standing fetal ascites and fresh intraperitoneal meconium at laparotomy, postoperative progress was uneventful. The baby did not have other dysmorphic features except for a single palmar crease, the chromosomes were normal, and the baby did not have cystic fibrosis. Follow-up examination at 10 months showed a thriving infant with mild hypotonia and developmental delay, but no respiratory or gastrointestinal problems.

Studies on the sex ratio of worms in schistosome infections.

Sex ratios of adult schistosomes in mice are almost invariably different from 1.0 and are biased towards males. The bias applies to wild rats infected with Schistosoma japonicum and trapped in an endemic area of the Philippines (male:female ratio = 1.7). It also applies to cercariae of snails collected in such areas and assessed by infection of laboratory mice using cercariae from individual snails (male:female ratio may approach 6.0). Experiments were designed to determine if duration of infection in the mammalian host was a factor that influenced the sex ratio of miracidia used for infecting snails and subsequently mice. BALB/c and C57BL/6 mice were infected with 100 cercariae of S. mansoni, and liver eggs harvested at early and late time points for infection of snails and production of cercariae. Two phenomena were demonstrated: firstly, a more pronounced male bias when eggs were harvested late compared with early in infection; secondly, a reduced apparent hatchability of eggs in BALB/c compared with C57BL/6 livers. The possibility is raised by the data that female miracidia within eggs of chronically infected individuals may be more prone to immune damage than male miracidia with important epidemiological consequences.

Effects of induction of anti-embryonation immunity on liver granulomas, spleen weight and portal pressure in mice infected with Schistosoma japonicum.

BALB/c mice sensitized with injections of viable immature Schistosoma japonicum eggs had significantly fewer and smaller granulomas in the liver, lower portal pressure and smaller spleens at D + 75 of infection compared to similarly infected unsensitized controls. The portal pressure and spleen weights of the mice sensitized with immature eggs were not different from uninfected unsensitized mice of similar ages at D + 75 of infection. The results strongly support our hypothesis that it should be possible to prevent serious hepatosplenic disease in schistosomiasis japonica by vaccination to induce anti-embryonation immunity.

Evidence of anti-embryonation immunity and egg destruction in mice sensitized with immature eggs of Schistosoma japonicum.

BALB/c mice sensitized by repeated injections of immature eggs of the trematode worm, Schistosoma japonicum, were challenged with low numbers of cercariae and evidence was sought for inhibition of embryonation by examination of eggs in livers and intestines at days 40 - 42 of infection. In contrast to the situation in unsensitized control mice, a greater proportion of dead eggs was noted in tissues of many of egg-sensitized mice. There was also a decrease in the proportion of mature eggs relative to control mice. A substantial number of egg - sensitized mice contained no eggs in the liver though eggs were readily detected in their intestinal walls. The data support the concept that immune effector mechanisms act on eggs in a manner that prevents their full development into a miracidium and thus a rich source of immunopathologic antigens.

Comparison of lidocaine and 2-chloroprocaine in paracervical block: clinical effects and drug concentrations in mother and child.

2-Chloroprocaine (CP) has recently been recommended as a less toxic alternative to amide-type local anesthetics due to its rapid metabolism. A double-blind, randomized study comparing CP to lidocaine when used for paracervical block was carried out. Twenty-nine patients received CP, while 31 received lidocaine. None of the 60 mothers developed adverse side effects. Adequate pain relief was achieved in 28 cases in each group, with a mean duration of 40 min regardless of the anesthetic. No change in uterine activity was observed. In the CP group one fetus had mild bradycardia, while two in the lidocaine group had severe, and three mild bradycardia within 5-7 min after the block. Low concentrations of CP were detected in the venous blood of 2 of 29 mothers and in the umbilical venous blood of their babies. Measurable amounts of its metabolite, 2-chloro-4-aminobenzoic acid (CABA), were found in all 13 samples of maternal blood 5 min after PCB and in 6 of 27 maternal samples at birth. Traces of CABA were found in umbilical venous blood in three neonates; in a fourth, a level of 1,000 ng/ml was found. In contrast, unmetabolized lidocaine was found in all maternal samples and in all but one of the cord samples at birth. Concentration of lidocaine in cord blood at delivery ranged from less than 100 to 4,000 ng/ml and were similar for both arterial and venous samples. No correlation could be demonstrated between levels of local anesthetics in the cord samples and the frequency or severity of fetal bradycardia regardless of the anesthetic.

Early prenatal diagnosis of soft-tissue malformations.

This study presents 3 cases of severe soft-tissue malformations of the fetus. Prenatal diagnosis was established early in the second trimester, and the accuracy of the diagnosis was confirmed by pathological examination in each instance. A clinically oriented work-up plan for early prenatal diagnosis is proposed.