Gregory F. Glasscock

Once-daily gentamicin dosing in newborn infants

Objective. We developed a simplified gentamicin dosing protocol for all neonates using a loading dose and once-daily dosing that would have an equal or lower incidence of toxicity and an equal or improved effectiveness compared with a regimen with no loading dose that included use of divided daily dosing. Methods. All neonatal intensive care unit patients with a postnatal age ≤7 days and started on gentamicin therapy at the discretion of the attending neonatologist were evaluated in this comparative cohort study. All peak and trough serum drug levels (SDL), pertinent demographic data, and markers of potential nephrotoxicity, ototoxicity, and cure were tracked prospectively during 132 consecutive, nonrandomized courses of therapy on a new gentamicin protocol. These were compared with data retrieved retrospectively throughout 103 consecutive, nonrandomized courses of therapy in a control group. Results. Initial measured peak SDL were higher (7.8 ± 1.1 μg/mL vs 6.1 ± 1.0 μg/mL) and trough SDL were lower (0.9 ± 0.2 μg/mL vs 2.7 ± 0.6 μg/mL) in the protocol term subset, compared with the control term subset (gestational age, ≥37 weeks; weight, ≥2500 g). One hundred percent of the initial and maintenance peak SDL in term protocol neonates were 5 to 12 μg/mL; compared with 84% of the initial and 61% of maintenance peak SDL in the term control group. One hundred percent of the initial and maintenance trough SDL were in the desired range of <2 μg/mL in term protocol neonates; compared with 70% of the initial and 94% of maintenance trough SDL in the term control group. No significant differences were found in any SDL in low birth weight neonates (gestational age <37 weeks or weight <2500 g and >1500 g) in the protocol compared with the control group. The very low birth weight (weight <1500 g) protocol neonates had a significantly higher mean initial trough SDL (2.3 ± 0.7 μg/mL vs 1.5 ± 0.6 μg/mL) and a lower incidence of initial trough SDL <2.0 μg/mL (30% vs 95%) than very low birth weight neonates in the control group. No differences were seen between groups in incidence of significant rise in serum creatinine or failure of hearing screen. Conclusion. A loading dose followed by once-daily dosing was shown to result in SDL in the safe and therapeutic range in all term neonates in this study. In low birth weight neonates, this regimen resulted in peak and trough SDL throughout therapy that were similar to those observed in the control group. Delaying the initiation of maintenance once-daily dosing until 36 to 48 hours after the loading dose would be expected to result in a higher incidence of initial trough SDL in target range for very low birth weight neonates.

Evidence for pituitary regulation of somatic growth, insulin-like growth factors-I and -II, and their binding proteins in the fetal rat.

ABSTRACT: We investigated pituitary regulation of late-gestation fetal growth in the spontaneous dwarf rat, a strain with an autosomal recessive mutation (gene symbol dr) in the growth hormone (GH) gene resulting in complete isolated GH deficiency. GH-normal/GH-deficient (Dr/dr) females were crossed with Dr/dr or dr/dr males, producing both GH-deficient and GH-normal fetuses within the same litter. Pups were killed within 3 h after birth to approximate the developmental state of a late-gestation fetus. The body weight of GH-deficient fetuses was inhibited by 14% in comparison to GH-normal animals, but tail length remained unaffected. The brain and lungs were the only organs whose growth appeared to be pituitary-independent. Other organs showed moderate pituitary dependence in proportion to body weight. Serum IGF-I and IGF-II were reduced by 73% and 52%, respectively, in the absence of GH. The major IGF-binding proteins (IGFBP) were analyzed by Western ligand blot. The predominant 26- to 30-kD IGFBP band normally seen in neonatal rat serum was greatly increased in GH-deficient sera, to 250% of GH-normal sera as measured by densitometry. However, addition of α-Hec 1 antibody to IGFBP-2, which has been used to identify IGFBP-2 as the major neonatal IGFBP, resulted in immunoprecipitation of only a small amount of the 26- to 30-kD band from the GH-deficient fetuses, suggesting the presence of an additional IGFBP. Northern analysis of GH-deficient livers did not reveal any visible increase in IGFBP-1, IGFBP-2, or IGFBP-4 mRNA. We conclude that pituitary GH exerts a modest, but significant, selective effect on fetal body weight and organ growth. Serum levels of both IGF-I and IGF-II, as well as their binding proteins, were shown to be pituitary-GH–dependent in the fetal period. The increase of low-molecular-weight binding proteins in the GH-deficient fetus, which we were unable to attribute to IGFBP-1, -2, -3, or -4, may indicate the presence of unique fetal binding protein(s). The spontaneous dwarf rat may be an important model for further investigation of the development of pituitary dependence in fetal growth.

Concomitant Branching Enzyme and Phosphorylase Deficiencies. An Unusual Glycogenosis with Extensive Neuronal Polyglucosan Storage

A baby girl was born hypotonic and was respirator-dependent until death at 43 days of age. A muscle biopsy revealed PAS-positive, diastase-resistant sarcoplasmic inclusions with a vaguely fibrillar structure by electron microscopy. Biochemical studies at autopsy disclosed complete absence of branching enzyme in skeletal muscle and heart, and a deficiency of phosphorylase activity in skeletal muscle with a modest reduction in myocardium. Storage material was present in glia and perikarya of neurons, increasing in amount in the rostrocaudal direction, involving most severely the motor neurons in the brain stem and spinal cord, dorsal root ganglia and myenteric plexi. Inclusions were also present in most organs, especially liver and skeletal muscle. Ultrastructurally, the inclusions ranged from granular aggregates of membrane-bound material concentrated in the region of Golgi apparatus to large filamentous bodies similar to polyglucosan bodies. This baby differs from other patients with infantile glycogenosis IV by the severity and onset of symptoms at birth, involvement of neuronal perikarya and widespread extraneural deposits. The combined deficiencies of branching enzyme and phosphorylase may have accounted for the unique clinical and neuropathological findings.

Adhesion of Percutaneously Inserted Silastic Central Venous Lines to the Vein Wall Associated With Malassezia furfur Infection

Percutaneously inserted Silastic central venous catheters have been used for prolonged infusion of parenteral nutrition in neonates. Malassezia furfur infection has been associated with intravenous fat emulsions infused through central venous lines. In this paper, we report two premature infants whose Silastic catheters were adhered to the vein wall with associated M furfur infection.

The Zavanelli maneuver for relief of abdominal dystocia associated with gastroschisis

A patient with acute hydramnios and advanced preterm labor at 34 weeks was seen after gastroschisis had been diagnosed by second-trimester fetal ultrasonography. The fetus also had meconium peritonitis and acute ascites. The distended abdomen did not decompress spontaneously during the second stage of labor. Severe abdominal dystocia was resolved with the Zavanelli maneuver (cephalic replacement) and cesarean delivery. This is the first reported use of the Zavanelli maneuver for abdominal dystocia.