Treatment of distal ureteral stones in children: similarities to the american urological association guidelines in adults.

PURPOSE: The American Urological Association (AUA) published clinical guidelines for the treatment of ureteral calculi in adults and note that up to 98% of stones less than 5 mm. in diameter will pass spontaneously. Ureteroscopy and shock wave lithotripsy were acceptable treatment choices for stones less than 10 mm. in diameter in the distal ureter. We reviewed our management of distal ureteral stones in children to see if the AUA Guidelines for adults would apply. MATERIALS AND METHODS: A total of 14 males and 19 females with a mean age of 12 years (range 0.5 to 17) required hospitalization in the last 6 years for distal ureteral obstruction due to stones. Excretory urography or computerized tomography was performed in all cases, and mean stone size was 4 mm. (range 1 to 15). When stones did not pass spontaneously most patients were treated with ureteroscopic laser lithotripsy. RESULTS: There were 12 (36%) with a mean age of 11 years and a mean stone size of 2 mm. (range 1 to 3) who passed stones spontaneously with intravenous hydration and narcotics. No child passed a stone 4 mm. or greater spontaneously in this series. Of 21 patients (64%) with a mean age of 12 years and a mean stone size of 5 mm. (range 1 to 15) 2 were treated with ureteral stents, 17 with ureteroscopic lithotripsy and 2 with shock wave lithotripsy. All patients were stone-free at the end of the procedures. The stone composition was predominantly calcium oxalate. Mean followup was 2 years. CONCLUSIONS: Similar to the AUA guidelines in adults, most stones less than 3 mm. in diameter in the distal ureter of children will pass spontaneously. Stones 4 mm or greater in the distal ureter are likely to require endosurgical treatment. Ureteroscopy and shock wave lithrotripsy have a high success rate for stones between 4 and 15 mm. in the distal ureter. Needle ureteroscope and laser lithotripsy have allowed more stones to be treated safely and effectively in smaller children.

Genotypic analysis of a cluster of systemic Candida albicans infections in a neonatal intensive care unit.

Five very low birth weight infants developed systemic Candida albicans infection during a 6-week period in an urban neonatal intensive care unit. In an effort to assess whether a common source outbreak was present, the genomic DNA of the clinical isolates was compared by EcoRI and XbaI restriction fragment analysis and Southern blot hybridization with 27A, a species-specific, transposon-like probe. Although the restriction fragment analysis suggested strong similarities among the isolates, the hybridization patterns demonstrated that all strains were genotypically distinct. The parallel use of at least two restriction enzymes was important for differentiating the isolates. Rapid genotypic analysis of clinical isolates from a cluster of C. albicans infections permits determination of whether a common source is probable, facilitates epidemiologic decisions and may reduce infection control measures and attendant costs.

v-src induction of the TIS10/PGS2 prostaglandin synthase gene is mediated by an ATF/CRE transcription response element.

We recently reported the cloning of a mitogen-inducible prostaglandin synthase gene, TIS10/PGS2. In addition to growth factors and tumor promoters, the v-src oncogene induces TIS10/PGS2 expression in 3T3 cells. Deletion analysis, using luciferase reporters, identifies a region between -80 and -40 nucleotides 5' of the TIS10/PGS2 transcription start site that mediates pp60v-src induction in 3T3 cells. This region contains the sequence CGTCACGTG, which includes overlapping ATF/CRE (CGTCA) and E-box (CACGTG) sequences. Gel shift-oligonucleotide competition experiments with nuclear extracts from cells stably transfected with a temperature-sensitive v-src gene demonstrate that the CGTCACGTG sequence can bind proteins at both the ATF/CRE and E-box sequences. Dominant-negative CREB and Myc proteins that bind DNA, but do not transactivate, block v-src induction of a luciferase reporter driven by the first 80 nucleotides of the TIS10/PGS2 promoter. Mutational analysis distinguishes which TIS10/PGS2 cis-acting element mediates pp60v-src induction. E-box mutation has no effect on the fold induction in response to pp60v-src. In contrast, ATF/CRE mutation attenuates the pp60v-src response. Antibody supershift and methylation interference experiments demonstrate that CREB and at least one other ATF transcription factor in these extracts bind to the TIS10/PGS2 ATF/CRE element. Expression of a dominant-negative ras gene also blocks TIS10/PGS2 induction by v-src. Our data suggest that Ras mediates pp60v-src activation of an ATF transcription factor, leading to induced TIS10/PGS2 expression via the ATF/CRE element of the TIS10/PGS2 promoter. This is the first description of v-src activation of gene expression via an ATF/CRE element.

Metal-dependent binding of a nuclear factor to the rat metallothionein-I promoter.

Genomic footprinting studies in vivo and experiments using synthetic metal regulatory elements (MREs) in vitro suggest protein binding to the MREs of the mouse and rat metallothionein I (MT-I) genes. Using gel-retardation assays of promoter fragments, we observe a cadmium-dependent binding factor for the rat MT-I promoter in rat hepatoma cells. This factor is present in extracts from both uninduced and cadmium-induced cells, but requires the presence of cadmium to bind to the promoter. The formation of a cadmium-dependent complex is competed by an oligonucleotide containing two MREs. This competition is lost when when one of the MREs is mutated, indicating a requirement for at least two MREs for binding of this factor. The cadmium-dependent factor dissociates more rapidly from the MT-I promoter than does a factor that binds to a consensus Sp1 site present on the same DNA fragment. UV crosslinking analysis using nuclear extracts from cadmium induced cells, in the presence of an oligonucleotide probe containing both 5-bromodeoxyuridine and 32P-deoxycytidine, identifies a 39 kDalton protein associated with the metal inducible complex.

Metal-dependent binding of a factor in vivo to the metal-responsive elements of the metallothionein 1 gene promoter.

Using the technique of genomic footprinting, we demonstrate cadmium-inducible protection from dimethyl sulfate (DMS) modification of guanine residues in vivo in five metal-responsive elements (MREs) in the promoter of the rat metallothionein 1 (MT-1) gene. We also identify a site of extreme DMS hyperreactivity which, like the MRE protection, occurs only after metal ion induction. With this hyperreactive site as an indicator, we can measure the kinetics of induction and deinduction. Changes in the intracellular metal ion concentrations are reflected in alterations in the reactivity with DMS of guanine residues in the MT-1 gene promoter. Lastly, for both control and metal-induced cells, we observe DMS protection and enhancement of a binding site (located 5' of the distal MRE) which is a consensus sequence for the Sp1 transcription factor. Transfection experiments with deletion mutations of a fusion gene construct indicate both that a sequence region which includes this GC box regulates the basal level of expression of the MT-1 gene and that increasing the number of MREs in the promoter increases the induced level of transcription. Our genomic footprinting and transfection data together suggest that (i) a transcription factor, possibly Sp1, plays an important role in regulating the basal level of expression of the MT-1 gene and (ii) metal induction involves the metal-dependent binding to a sequence-specific binding factor which responds to changes in intracellular metal ion levels.

Magnetic resonance imaging of the brain in childhood herpesvirus infections.

We used magnetic resonance imaging (MRI) to evaluate nine children with neurologic disorders caused by infections with members of the herpesvirus family. MRI studies were abnormal in eight children and demonstrated a wide range of central nervous system lesions, including cystic encephalomalacia, ventricular enlargement, cerebral atrophy and focal parenchymal lesions. When compared with conventional computed tomographic scanning, MRI was more sensitive in detecting abnormalities of white matter and in defining the extent of parenchymal lesions. These studies indicate that MRI scans are highly useful in children with herpesvirus infections involving the central nervous system.

Herpes simplex virus infection of the neonatal respiratory tract.

Three patients with neonatal herpes simplex virus (HSV) infection with upper or lower respiratory tract involvement are described. In all three patients, fever and respiratory tract symptoms were the presenting features and occurred in the absence of mucocutaneous lesions or maternal history of HSV Infection. In none of the children was HSV Infection considered likely at the time viral cultures were obtained. These patients demonstrate the need for consideration of HSV in the evaluation of neonatal respiratory tract disease, particularly if it is accompanied by fever and presents after the first several days of life.

Acute viral laryngotracheitis complicated by herpes simplex virus infection.

We report the development of HSV-1 laryngotracheitis during the resolution phase of typical viral laryngotracheobronchitis (LTB) in an infant. This case represents an uncommon complication of viral LTB which has previously been described only at autopsy and suggests that prolonged use of systemic corticosteroids may lead to secondary infections, such as HSV-1. Therefore, we recommend that corticosteroid therapy for LTB be limited to 48 degrees in duration. This case also demonstrates that when an atypical clinical course is being followed by a patient who has LTB, then early diagnostic intervention is indicated. If HSV-1 is identified, anti-viral chemotherapy should be initiated and artificial airway management may be necessary. Tracheal intubation may be used, but, if extensive subglottic ulceration occurs, the subglottis should be bypassed in order that the chance of subglottic stenosis be minimized. In this case, early identification by bronchoscopy and viral cultures resulted in a successful combined medical-surgical management and total resolution with no sequelae.

Rat metallothionein multigene family.

Southern blot analysis of rat genomic DNA reveals the presence of numerous sequences homologous to the rat MT-1 gene. We have isolated and characterized by sequence analysis the rat MT-1 gene and three related processed pseudogenes. We discuss mechanisms by which these pseudogenes were formed. The rat MT-1 and MT-2 structural genes are shown to be separated by 4 kb of intergenic DNA. By sequence analysis of the MT-2 structural gene, we compare features of the MT gene sequences which regulate promoter activity, and which specify transcription termination and polyadenylation. From an examination of homologous sequences in the MT promoters, we suggest that there may be both regulatory features in common with the MT gene isotypes, and regulatory mechanisms which may allow for differential expression of these genes. We discuss possible applications of recombinant DNA technology to investigating both the expression of MT genes and the functioning of MT proteins, in a tissue specific manner and during development.

Intrauterine herpes simplex infection resembling mechanobullous disease in a newborn infant.

We present a case of transplacentally acquired intrauterine herpes simplex virus infection in a newborn delivered at 36 weeks' gestation by cesarean section because of intrauterine growth retardation and maternal preeclampsia. The mother experienced a single episode of serotype 2 herpes progenitalis at 14 weeks' gestation. At birth the infant manifested clinical findings of herpes simplex virus infection, which resembled epidermolysis bullosa and aplasia cutis congenita. Preexisting cutaneous lesions and intact fetal membranes at delivery strongly support a transplacentally acquired intrauterine herpes simplex virus infection. Repeated Tzanck smears, viral cultures, and immunohistochemical studies of the skin were required to confirm the diagnosis. Intrauterine herpes simplex virus infection is associated with significant morbidity and mortality but responds to antiviral therapy. Therefore this diagnosis must be considered in the neonate born with bullous or eroded skin lesions.

Rat metallothionein-1 structural gene and three pseudogenes, one of which contains 5'-regulatory sequences.

As shown by Southern blot analysis, the metallothionein-1 (MT-1) genes in rats comprise a multigene family. We present the sequence of the MT-1 structural gene and compare its features with other metallothionein genes. Three MT-1 pseudogenes which we sequenced apparently arose by reverse transcription of processed mRNA transcripts. Two of these, MT-1 psi a and MT-1 psi c, are retrogenes which derive from the MT-1 mRNA, having diverged from the MT-1 gene 6.9 and 2.6 million years ago, respectively. The third, MT-1 psi b, differs from the MT-1 cDNA by only three nucleotide alterations. Surprisingly, MT-1 psi b also preserves sequence homology for 142 base pairs 5' to the transcription initiation site of the parent gene; it contains a promoter sequence sufficient for specifying metal ion induction. We identified, by S1 nuclease mapping, an RNA polymerase II initiation site 432 base pairs 5' of the MT-1 transcription initiation site of the MT-1 structural gene which could explain the formation of the mRNA precursor to this pseudogene. We were unable to detect MT-1 psi b transcripts, either in liver tissue or after transfection. We conclude that the absence of detectable transcripts from this pseudogene is due to either a reduced level of transcription or the formation of unstable transcripts as a consequence of the lack of a consensus sequence normally found 3' of transcription termination in the MT-1 structural gene.

Metoclopramide given pre-operatively empties the stomach.

Sixty adult patients admitted for emergency major orthopedic surgery were studied according to a double-blind, randomized design in order to evaluate if a single dose of 20 mg metoclopramide given intravenously at least 90 min before premedication could evacuate the stomach before anesthesia. Three patients were excluded. X-ray examination following intake of barium sulfate before anesthesia showed 10 patients with a full stomach, all belonging to the placebo group. This study demonstrates significantly fewer (P less than 0.002) patients with a full stomach before anesthesia after metoclopramide, indicating that administration of metoclopramide reduces the risk of aspiration of gastric contents to the lungs during anesthesia.

Virus-induced leukopenia: Colorado tick fever as a human model.

Eight patients with Colorado tick fever were studied to determine whether alterations in the production of granulopoietic stimulatory or inhibitory factors (or both) could be found in association with the leukopenic state of the disease. The studies demonstrate that in the patients with Colorado tick fever the mononuclear cell production of colony-stimulating factor is decreased and that there is an increase in circulating inhibitory factors in the serum of such patients. The depressed mononuclear cell colony-stimulating activity does not appear to be reversible by addition of either endotoxin or normal human serum. Characterization of these serum inhibitory factors may facilitate understanding of leukopenia in human disease.

Mycoplasma pneumoniae and Nocardia asteroides in lung biopsy tissue of an immunodeficient infant.

Mycoplasma pneumoniae and Nocardia asteroides were recovered from lung tissue of an infant with an immunologic deficit. The isolate suggests a possible role of M. pneumoniae as an opportunistic pathogen. This case underscores the importance of comprehensive evaluation of lung biopsy specimens and the usefulness of Mycoplasma cultures.

Mutations affecting the regulation of transcription of the cytochrome P1-450 gene in the mouse Hepa-1 cell line.

The cytochrome P1-450-dependent activity, aryl hydrocarbon hydroxylase, and cytochrome P1-450 messenger RNA levels were studied in wild-type Hepa1c1c7 cells and in aryl hydrocarbon hydroxylase-deficient mutants derived from this line. Tetrachlorodibenzo-p-dioxin (TCDD) induced both parameters approximately 50-fold in Hepa1c1c7 cells. Mutants in genes B and C that are affected in the functioning of the Ah receptor required for hydroxylase induction and dominant mutants had nondetectable or much reduced P1-450 mRNA levels and hydroxylase activities after TCDD treatment. Hybrids between wild-type cells and the dominant mutants were also deficient in these parameters. The dominant mutants therefore appear to express a trans-acting repressor of cytochrome P1-450 transcription. Mutants in gene A were heterogenous. Some lacked the mRNA completely; others were inducible for it; while still others (subgroup IV) had high levels even when they were grown without TCDD. These results suggest strongly that gene A is the structural gene for cytochrome P1-450. When subgroup IV mutants were cultured together with wild-type cells, they failed to express P1-450 mRNA in the absence of TCDD treatment. These cells probably accumulate an inducer that can be metabolized by aryl hydrocarbon hydroxylase. The inducer did not appear to be a component of the medium and therefore may be an endogenous ligand of the Ah receptor.