Chloral hydrate sedation of children undergoing CT and MR imaging: safety as judged by American Academy of Pediatrics guidelines.

OBJECTIVE: The purpose of this prospective study was to determine the frequency of adverse events associated with supplemented and unsupplemented chloral hydrate sedation in a select group of children undergoing CT or MR imaging using the revised American Academy of Pediatrics (AAP) monitoring and management guidelines for pediatric sedation. The AAP guidelines do not recommend drug selection or dosages but define patient selection, discharge criteria, and monitoring standards for sedating children. SUBJECTS AND METHODS: This prospective study included 410 children 4 years of age or younger who were scheduled for CT and MR imaging as outpatients. Selected children were physical status 1 or 2 as determined by the American Society of Anesthesiologists physical status classification and had no contraindications to sedation per our institutional sedation policy. Children younger than 1 year old received only oral incremental doses of chloral hydrate. Children 1-4 years old received hydroxyzine plus incremental doses of chloral hydrate. Children between 2 and 4 years old who were not satisfactorily sedated 30 min after hydroxyzine plus incremental chloral hydrate were given 2 mg/kg meperidine intramuscularly, with a maximum dose of 50 mg. All children were monitored according to the revised guidelines recommended by the committee on drugs of the AAP. Vital signs and arterial hemoglobin oxygen saturation (SpO2) were monitored continuously by registered nurses trained in pediatric advanced life support from the time of sedative drug administration until the recommended discharge criteria were met. RESULTS: Mild hypoxia (SpO2, 90-95%) that resolved spontaneously without any therapeutic intervention was seen in 9% of the chloral hydrate group and in 5% of the chloral hydrate-hydroxyzine group. One child in the chloral hydrate group had severe hypoxia (SpO2, 85-89%), and one child in the chloral hydrate-hydroxyzine group had moderate hypoxia (SpO2, < 85%). Both required therapeutic intervention. In both cases, the severity of the underlying medical disease was underestimated at the time of presedation medical screening. The success rate of sedation was 100% for all the children having CT. For those having MR imaging, success was 100% for children 1-4 years old and 97% for children less than 1 year old. CONCLUSION: Use of supplemented and unsupplemented chloral hydrate sedation provides effective and safe sedation in children if the AAP guidelines for patient selection, monitoring, and management are followed. Careful medical screening and patient selection by knowledgeable medical personnel is important to exclude patients at high risk for life-threatening hypoxia. Monitoring with AAP guidelines is essential for prompt detection and management of life-threatening hypoxia.

Tissue-specific pharmacology of testosterone and 5 alpha-dihydrotestosterone analogues: characterization of a novel canine liver androgen-binding protein.

The mechanism by which the hormones 5 alpha-dihydrotestosterone and testosterone differentially regulate such diverse functions as development of male internal and external genitalia and maintenance of prostatic growth via a single androgen receptor (AR) is not well understood. To search for potential AR isoforms, an extensive pharmacological survey of the binding of [3H]mibolerone (7 alpha,17 alpha-[3H]dimethyl-19-nortestosterone) in dog prostate, adrenal gland, testis, liver, kidney, brain, muscle, and spleen cytosolic extracts was carried out. The antagonist androst-4-en-3,17-dione (ATD), as well as a series of unsaturated analogues of testosterone, exhibited marked tissue specificity for binding to mibolerone-binding proteins (MBPs), with ATD having a 10-fold higher affinity for the MBPs present in liver than for those in prostate and testis. The difference in affinity was not due to tissue-specific metabolism of ATD. Competition binding profiles for ATD with mixtures of prostate and liver extracts were consistent with two distinct populations of binding sites. Both wild-type human AR-B and the recently discovered human AR-A isoform were expressed in COS cells and were found to exhibit pharmacology similar to that of the prostatic MBPs in dogs. Analogues of ATD or testosterone could prove to be useful probes for delineating the differential effects of 5 alpha-dihydrotestosterone and testosterone on the biological actions of the AR and related proteins.

Prolidase deficiency: a multisystemic hereditary disorder.

Prolidase deficiency is a rare hereditary disorder with a wide spectrum of clinical manifestations including skin ulcers, eczematous eruptions, characteristic facies, mental retardation, splenomegaly, and susceptibility to infections. We report two new cases of prolidase deficiency. Our patients had the typical manifestations of prolidase deficiency. One also had lupus erythematosus. Prolidase activity was either normal or half-normal in all family members. The skin disease in our patients did not respond to topical glycine/proline ointment or to oral vitamin C.

Prolidase deficiency in cultured human fibroblasts: biochemical pathology and iminodipeptide-enhanced growth.

Prolidase deficiency is a rare autosomal recessive disorder characterized by iminodipeptiduria, severe skin ulcers, recurrent infections, and mental retardation. The enzyme prolidase hydrolyzes dipeptides containing C-terminal proline or hydroxyproline. We investigated the metabolic abnormality caused by prolidase deficiency in human cultured skin fibroblasts. These studies were undertaken to test biochemical hypotheses regarding the metabolic origins of the skin lesion occurring in this disease. Our results indicate that prolidase plays a major role in the recycling of dipeptide-bound proline. Control fibroblasts were able to use iminodipeptides in lieu of proline to sustain normal growth, whereas cells homozygous for the prolidase deficiency mutation were not. Proline derived from iminodipeptides diluted incorporation of radiolabeled extracellular proline into cellular protein in normal cells but not in mutant cells. Substitution of a prolidase-free medium for FCS did not affect the growth rate of control cell lines but increased the doubling time of prolidase-deficient cells by 19% (28% in the presence of iminodipeptides). Iminodipeptides added to control and mutant cells maintained in serum-free medium showed no adverse effects on protein synthesis. These results are consistent with a mechanism of biochemical pathology in which proline deprivation caused by the enzyme deficit is a primary cause of damage to skin cells. Prolidase regulation by product and substrate was studied. A 44% decrease in activity was observed in fibroblasts grown for 3 wk in proline-containing medium relative to proline-free medium. However, cells grown in medium in which iminodipeptides replaced proline showed no significant difference in prolidase activity.