Management of high grade renal trauma: 20-year experience at a pediatric level I trauma center.

PURPOSE: In the last 20 years the management of high grade, blunt renal trauma at our institution has evolved from primarily an operative approach to an expectant nonoperative approach. To evaluate our experience with the expectant nonoperative management of high grade, blunt renal trauma in children, we reviewed our 20-year experience regarding evaluation, management and outcomes in patients treated at our institution. MATERIALS AND METHODS: We retrospectively studied all patients sustaining renal trauma between 1983 and 2003. Medical records were reviewed for mechanism of injury, assigned grade of renal injury, patient treatment, indications for and timing of surgery, and outcome. Injuries were categorized as either low grade (I to III) or high grade (IV to V). RESULTS: We reviewed the medical records of 164 consecutive children who sustained blunt renal trauma between 1983 and 2003. A total of 38 patients were excluded for inadequate information. Of the remaining 126 children 60% had low grade and 40% had high grade renal injuries. A total of 11 patients (8.7%) required surgical or endoscopic intervention for renal causes, including 2 for congenital renal abnormalities and 1 for clot retention. Eight patients (6.3%) required surgical intervention for isolated renal trauma, of whom 2 (1.6%) required immediate surgical intervention for hemodynamic instability and 6 (4.8%) were treated with a delayed retroperitoneal approach. Only 4 patients (3.2%) required nephrectomy. All patients receiving operative intervention had high grade renal injury. CONCLUSIONS: Initial nonsurgical management of high grade blunt renal trauma in children is effective and is recommended for the hemodynamically stable child. When a child has persistent symptomatic urinary extravasation delayed retroperitoneal drainage may become necessary to reduce morbidity. Minimally invasive techniques should be considered before open operative intervention. Early operative management is rarely indicated for an isolated renal injury, except in the child who is hemodynamically unstable.

A preliminary multi-stable-isotopic evaluation of three synthetic pathways of Topiramate.

As a preliminary study of the utility of the natural stable-isotopic differentiation of batch samples produced by different synthetic pathways, multi-stable-isotopic analyses (delta(13)C, delta(15)N, delta(18)O, deltaD) of 53 samples of the antiepileptic drug, Topiramate, produced by three different synthetic pathways (designated "A," "B," "C") were performed. From the outset, we note that there are two fundamental variables that determine the stable-isotopic composition of materials-the stable-isotopic composition of the reagents and starting intermediates, and the isotope fractionation that occurs during manufacture of the product. In this study, the stable-isotopic composition of the raw materials was not controlled and we report here data obtained for a suite of samples that was produced by three synthetic pathways. Graphical examination of these data reveals marked data clustering by synthetic pathway, though in some cases with some overlapping values within standard errors. In general, the isotopic composition of Topiramate from the A and B pathways is distinct from the C pathway. The isotopic data from the A and B pathways typically abut each other, sometimes partially overlapping. The deuterium/hydrogen- (deltaD) and oxygen (delta(18)O) isotopic compositions are each significantly linearly related with the paired carbon (delta(13)C) isotopic composition indicating possible isotopic end-members for the raw materials of the present sample suite. Given that H and O typically derive from meteoric water, the linear correlations with delta(13)C indicate that a mixture of carbon sources (viz., perhaps terrestrial C3 photosynthetic organic carbon and marine C3 organic carbon) were used in the production of the batches tested. If the H and O analyzed were derived from meteoric water, then an elementary comparison of the span of the deltaD (DeltadeltaD = 54.6 +/- 2.1 per thousand) and of the delta(18)O (Deltadelta(18)O = 4.71 +/- 0.26 per thousand) values in the Topiramate samples to that of the global isotopic gradients indicates that the water retained in the samples spanned from as much as 11 degrees of latitude (or, approximately 760 statute miles North-to-South). The present isotope results (delta(13)C, delta(15)N, delta(18)O, deltaD) form an initial database against which future samples can be compared to infer specific synthetic pathways. It is clear that to perform a rigorous test of the variables controlling the stable-isotopic composition of pharmaceutical materials that both the stable-isotopic composition of the starting materials and synthetic isotope fractionation must be controlled in future studies.

ECLS in pertussis: does it have a role?

OBJECTIVES: To investigate the value of extracorporeal circulatory life support (ECLS) in paediatric patients with severe Bordetella pertussis infection. DESIGN: Single case report and a review of the ECLS database. SETTING: Tertiary referral hospital paediatric intensive care unit. PATIENTS AND PARTICIPANTS: A single case report of an infant with B. pertussis infection is described. Despite receiving ECLS, this infant died from overwhelming cardiac and cerebral insults. Outcome for children receiving ECLS registered on the Extracorporeal Life Support Organization database is reviewed. MEASUREMENTS AND RESULTS: The mortality of infants receiving ECLS for B. pertussis infection is high, with only 5 survivors reported among 22 registered cases. The majority of nonsurvivors had evidence of circulatory collapse in addition to severe respiratory failure, and these patients commonly died of hypoxic-ischaemic cerebral insult. These data suggest the existence of a subgroup of patients with respiratory failure only, who may benefit from ECLS, and a larger subgroup who suffer ischaemic cardiac and cerebral insults which are unlikely to be improved by ECLS. CONCLUSIONS: The value of ECLS in patients with B. pertussis infection who present with major cardiac dysfunction is questionable. Such patients almost invariably have a poor outcome despite maximal therapy.

Pharmacokinetic-pharmacodynamic relationships of morphine in neonates.

Morphine pharmacokinetics and pharmacodynamics (analgesia and sedation) were evaluated after continuous intravenous infusion of morphine in 19 neonates, both preterm and term, whose lungs were ventilated to relieve respiratory distress. Elimination half-life, total plasma clearance, and volume of distribution (mean +/- SD) were 9.6 +/- 3.0 hours, 2.55 +/- 1.65 ml/min/kg (area analysis) or 2.09 +/- 1.19 ml/min/kg (steady-state data), and 2.05 +/- 1.05 L/kg, respectively, and were not significantly different in preterm and term neonates. In neonates with adverse effects of morphine, the plasma clearance was decreased twofold. Mean morphine concentration required to produce adequate sedation in 50% of patients was found to be 125 ng/ml, but concentrations above 300 ng/ml may be associated with adverse effects of morphine. Morphine-6-glucuronide was not detected in the plasma of any neonate, which may explain why neonates require high plasma concentrations of unchanged morphine for sedation.

Failure of intravenous infusions in neonates.

The median life expectancy (survival) of 286 peripheral intravenous infusion sites in 105 babies in a children's intensive care unit was 36 h. Unadjusted univariate survival analysis revealed that dextrose infusions and the initial infusions received by a baby had longer survival than total parenteral nutrition (TPN) infusions and later infusions respectively. Also infusions with cloxacillin and penicillin survived for longer than average while infusions with phenytoin had reduced survival. Gestational age, weight, infusion site, other drugs, co-infusion of Intralipid with TPN solutions and neutralization of TPN did not influence survival of infusions. Multivariate survival analysis confirmed the findings for TPN and penicillin but not for cloxacillin, phenytoin or later infusions. Multivariate analysis also suggested that survival was improved with ampicillin and aminophylline and worse for leg sites, for older babies and for infusions in which the fluids were given at greater rates. It also indicated that neutralization of TPN improved survival.

Phytanic acid oxidase deficiency in childhood.

Tables 2 and 5 summarize the major clinical and biochemical findings in these patients. Cases 1 and 2 resemble clinically the previous cases of children reported as suffering from infantile phytanic acid storage disease, Zellweger's disease, or neonatal adrenoleucodystrophy. Cases 3 and 4 differ strikingly from these and from one another. Numerous questions remain unanswered, but it seems likely that these patients have in common defects in peroxisomal function which are related but not identical. Why some patients with phytanic acid oxidase deficiency do not have significant elevation of serum phytanic acid is not known. These results, however, make it clear that a normal serum phytanic acid level does not exclude phytanic acid oxidase deficiency. In children with a progressive neurological illness, with liver disease, retinal disease, unexplained neuropathy or deafness, detailed studies of fatty acid metabolism are indicated, including lipoproteins, serum phytanic acid, C26:C22 long-chain fatty acid ratios, serum pipecolic acid and phytanic acid oxidase levels. Electron microscopy of liver biopsy specimens should be considered. Phytanic acid oxidase may prove a useful marker for some of these illnesses, and its usefulness could extend to prenatal diagnosis and assist in genetic counselling.

The effect of an energy-restricted diet on the protein metabolism of obese adolescents: nitrogen-balance and whole-body nitrogen turnover.

1. The effect of an energy-restricted (46 kJ day-1 kg-1), adequate protein diet (1.47 g day-1 kg-1) on the nitrogen metabolism of five obese rapidly growing adolescents (two males and three females) was assessed by means of nitrogen-balance measurements and determination of whole-body nitrogen turnover. 2. The energy-restricted diet had no significant effect on nitrogen balance (P more than 0.1) for the entire group when compared with the control dietary intake; however, significant (P less than 0.01) differences in nitrogen balance were noted among individuals at each dietary interval. 3. Mean values for whole-body nitrogen turnover, protein synthesis and breakdown for the control period were: 45.5 +/- 13.2 mg of nitrogen day-1 kg-1, and 5.72 +/- 1.96 and 5.74 +/- 1.92 g of protein day-1 kg-1 respectively. These values are 82% of those measured in infants. 4. Reducing the mean non-protein energy intake to 20 kJ day-1 kg-1 had no significant effect on whole-body nitrogen turnover, protein syn;thesis or protein breakdown. 5. The results are discussed in relation to the regulation of whole-body nitrogen metabolism, by dietary protein and energy intakes.

Synthesis of spiro[isobenzofuran-1(3H),4'-piperidines] as potential central nervous system agents.

Synthesis of 1'-methyl-3-phenylspiro[isobenzofuran-1(3H),4'-piperidine] (7a, HP 365) and the demethyl analogue 9a (HP 505) was prompted by recognition of an aminoalkyl(aryl)isobenzofuran moiety common to the antidepressants talopram (Lu 3-010) and trans-10,11-dihydro-5,10-epoxy-5-[3-(methylamino)propyl]-5H-dibenzo[a,d]cyclohepten-11-ol (MK-940). Convenient laboratory synthesis of 7a was provided by lithiation of 2-bromobenzhydryl methyl ether, followed by addition of 1-methyl-4-piperidone and acid-catalyzed cyclization. N-Dealkylation by standard methods afforded 9a. Synthesis of analogues was stimulated by discovery of marked inhibition of tetrabenazine-induced ptosis for lead compounds 7a and 9a. Optimal antitetrabenazine activity is associated with the 3-phenylspiro-[isobenzofuran-1(3H),4'-piperidine] moiety where nitrogen is basic. Modification of this moiety by introduction of large nitrogen substituents or a C-3 substituent greater than H significantly reduced antitetrabenazine activity. A series of analogues with aromatic substituents was investigated; however, few of these compounds were significantly more active than 7a and 9a. Compound 9a was selected for additional studies.

Recovery of spermatozoa from human vaginal washings.

Sperm survival, in terms of numbers, motility, viability, and metabolic activity, was studied in vaginal washings obtained daily from 22 healthy, fertile, married women during one complete menstrual cycle. The numbers of sperm (counted on Papanicolaou-stained filters) were never large compared to the number of sperm in a single ejaculate. Forty-eight hours after intercourse, only 6% of the specimens showed any evidence of sperm. Motile sperm were observed in only six of 94 postcoital specimens examined within 12 hours after intercourse. Lack of sperm in specimens collected after reported intercourse was associated with contraceptive practices other than the rhythm method, which most of the subjects were using. Fluorochromatic studies of recovered sperm treated with acridine orange indicated sperm viability and phase contrast studies of sperm treated with tetrazolium salts revealed metabolic activity. Our data on sperm motility, numbers, and staining reactions support the conclusion that the small number of sperm that remain in the vagina after intercourse quickly become inactivated.

PIP: Number, motility, viability, and metabolic activity of sperm were studied in vaginal washings obtained daily from 22 fertile, married women during 1 menstrual cycle. Sperm were recovered in 73% of the samples examined within 12 hours postcoitus. Motile sperm were observed in only 6 samples collected within 12 hours postcoitus. All sperm collected 24 hours postcoitus were nonmotile. Numbers of sperm ranged from 0 or very few to nearly 1/2 million/cubic cm. Most samples were in the range of 0-30000 3-36 hours postcoitus. Formazan-positive stain reactions observed in 5% of the samples were weak, indicating no metabolic activity. Nonmotile sperm showed some viability through green fluorescence in the acridine orange fluorochrome reaction. When data were adjusted for the use of contraceptive techniques other than rhythm (coitus interruptus, condom), sperm were recovered in almost every instance of reported coitus. It is concluded that the small number of sperm remaining in the vagina following coitus quickly become inactivated.