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Biomedical subjects

P Soucy

Publications and source records attributed to P Soucy.

At least 19 recordsLinked to original sources
PubMed2001

Comparative biosynthetic pathway of androstenol and androgens.

It has been shown recently that androstenol and androstanol could modulate gene expression through the nuclear orphan receptors CAR (constitutive androstane receptor) and PXR (pregnane X receptor). Although, in the pig, androstenol is produced in high amounts and is active as a pheromone, its role in the human is ill defined. Androstenol possesses a structure similar to that of androgens, with the exception that it does not possess an oxygen at position 17 that is crucial for androgenic and estrogenic activity. It has been shown that human and boar testis homogenates could produce androstenol, but details of the biosynthetic pathway had not yet been elucidated. It has also been shown recently that androstenol could modulate the activity of CAR and PXR and the expression of some cytochrome P450 drug-metabolizing enzymes. We wanted to determine the precise biosynthetic pathway of androstenol and other closely related steroids. Using transformed human embryonic kidney (HEK-293) cells that stably express 3 beta-hydroxysteroid dehydrogenase, 5 alpha-reductase and 3 alpha-hydroxysteroid dehydrogenase, we have shown that these enzymes are able to efficiently transform the precursor 5,16-androstadien-3 beta-ol into androstenol. We thus provided evidence that androstenol, the ligand for CAR and PXR, is produced by the biosynthetic pathway of sex steroids.

3-Hydroxysteroid Dehydrogenases↗
PubMed2001

Significance of the clinical course and early upper gastrointestinal studies in predicting complications associated with repair of esophageal atresia.

BACKGROUND/PURPOSE: In many centers, use of upper gastrointestinal (UGI) contrast studies in the early postoperative period after esophageal atresia (EA) repair is considered routine. Indications for this are many, including searching for existing problems and predicting future complications. However, most major complications, both early and late, usually are identified clinically before any radiologic studies. The purpose of this study was to investigate factors that may anticipate the development of postoperative complications after EA repair, looking particularly at the predictive value of routine early postoperative UGI studies. METHODS: A total of 111 consecutive cases of EA were identified retrospectively over a 10-year period from 2 major Canadian pediatric health centers. One hundred one were associated with a distal tracheoesophageal fistula (TEF), of which, 90 had repairs. Ninety-seven percent of these had a UGI study at a median of 9.1 postoperative days (range, 2 to 23) before consideration of oral feeding. Charts were reviewed looking at patient variables, surgical factors, early UGI findings, and postoperative courses. Complications that required intervention were noted, including anastomotic leaks, gastroesophageal reflux (GER), strictures, and recurrent and missed fistulae. All initial UGI studies were reexamined by 1 of 2 pediatric radiologists. Logistic regression was used to examine relationships between these clinical and radiologic variables and outcomes. RESULTS: Of the variables analyzed, univariate analysis showed clinically significant leaks to be associated with intraoperative factors (subjective degree of anastomotic tension, and the use of myotomies) and early postoperative clinical evidence suggesting a leak. In a multivariate model, all remained independently significant except for the use of myotomies. Later development of clinically significant GER also was associated with the degree of tension. It had no relationship, however, with findings of dysmotility, esophageal shortening, or reflux at the initial UGI study. Development of a stricture requiring dilatations or resection was associated with a history of clinically evident GER only; no relationships were seen with a history of an anastomotic leak or any other clinical, operative, or radiographic variables. Missed or recurrent fistulae were all suspected clinically before radiologic confirmation. CONCLUSIONS: Early and late complications after repair of EA can be identified and potentially anticipated based on clinical findings at the time of repair and during the postoperative period. The use of early "routine" UGI studies, with no suspicion of a problem, has little value in terms of predicting complications or future clinical course.

Analysis of Variance↗
PubMed2000

Conversion of pregnenolone to DHEA by human 17alpha-hydroxylase/17, 20-lyase (P450c17). Evidence that DHEA is produced from the released intermediate, 17alpha-hydroxypregnenolone.

Most previous studies using reconstituted systems and fast kinetics suggest that the conversion of pregnenolone to dehydroepiandrosterone (DHEA; the precursor of androgen and estrogen biosynthesis) by P450c17 does not require the release of the intermediate 17alpha-OHPreg (a precursor of cortisol biosynthesis). With such a mechanism, it is difficult to conceive how high amounts of DHEA may be produced in some cells or tissues, such as the testis and cells from the adrenal reticularis, while in other tissues such as the fasciculata zone, high levels of 17alpha-OHPreg are synthesized. In this report, we address this matter using intact transfected cells, which better reflect the actual cellular conditions. Furthermore, by using transfected cells, we can conveniently analyze human enzymes, as we are not restricted by the availability of human tissues as in the case of methods using purified or partially purified enzymes. Using intact HEK-293 cells transfected with human P450c17 in culture, we showed, in a time course study of the transformation of pregnenolone, that there is an accumulation of 17alpha-OHPreg, and that, subsequently, the accumulated 17alpha-OHPreg decreases with a concomitant increase in DHEA production. The DHEA/17alpha-OHPreg ratio changes from 0.1 :1 after 1 h incubation to 50 : 1 after 20 h. This result strongly suggests that the transformation of Preg to DHEA proceeds through two steps in which DHEA is produced from the released intermediate 17alpha-OHPreg. We also show that high levels of substrate vs. enzyme concentration will lead to high hydroxylase activity whereas the reverse will increase the lyase activity. The result is in good agreement with recent observations suggesting that surrounding enzymes and steroids could modulate the lyase activity. Cotransfection of vectors expressing cytochrome b5 and NADPH cytochrome P450 reductase indicates that both are required for an optimum production of DHEA.

17-alpha-Hydroxypregnenolone↗
PubMed2000

Subcutaneous granuloma annulare of the extremities in children.

OBJECTIVE: To familiarize surgeons to the natural history and treatment of granuloma annulare of the extremities in children. DESIGN: Case review and follow-up by appointment and questionnaire. SETTING: The Children's Hospital of Eastern Ontario, a tertiary referral centre. PATIENTS: Twenty-seven children (23 girls, 4 boys) seen between 1983 and 1998 with subcutaneous granuloma annulare, proven pathologically. The mean age at initial presentation was 8.3 years (range from 1.8 years to 16.7 years). The mean follow-up was 45 weeks (range from 1 week to 5 years). INTERVENTION: Biopsy excision of the lesions. OUTCOME MEASURES: The incidence multiple lesions, the commonest site of occurrence and the incidence of recurrence. RESULTS: Six children presented with multiple lesions for a total of 46 lesions. The anterior pretibial area was the most frequently affected site (16 lesions), followed by the ankle (6 lesions) and the long finger (4 lesions). Five patients suffered recurrence of the lesion, with a total of 7 lesions recurring. CONCLUSIONS: Subcutaneous granuloma annulare is a benign inflammatory skin lesion occurring most frequently in the anterior pretibial area in children, predominantly girls. The incidence of recurrence and of multiple lesions is high. Biopsy is required for definitive diagnosis. The lesion resolves spontaneously without treatment.

Adolescent↗
PubMed1999

Long-term outcome after Hirschsprung's disease: patients' perspectives.

BACKGROUND: The results of treatment of Hirschsprung's disease (HD) are not uniformly successful, and the parents' and child's interpretation of the outcome may be different from that of the surgeon. METHODS: One hundred seven children treated for HD over 22 1/2 years were reviewed retrospectively. Adequate clinical data regarding functional outcomes were available in 78, of which, an additional questionnaire was completed by 69. Follow-ups were divided into type of pull-through (PT), age at time of PT (< 4 months and > 4 months) and age at last follow-up (< 5 years, 5 to 15 years and > 15 years). Degrees of constipation and incontinence were determined using standard scoring systems. RESULTS: The median age at presentation was 9 days (range, 1 day to 9.4 years), and 41% presented within the first 72 hours of life. Aganglionosis extended to the rectosigmoid region in 75%, proximal to the splenic flexure in 11%, and total colon in 6.5%. Treatments included a Soave procedure in 57, Duhamel in 31, Swenson in 10, and sphincterotomy-myectomy in two. No surgical treatment or only a decompressing enterostomy was performed in two and three children, respectively, and two underwent a PT elsewhere. Complications related to the enterostomy occurred in 39 patients. Postoperative enterocolitis and bowel obstructions occurred in nine and 13 patients, respectively. Staple-line fusion, anastomotic stenosis, and anastomotic leak occurred in nine, 17, and two patients, respectively. Seven children died, only one directly related to the PT. Aside from more constipation associated with the Duhamel procedure, functional outcomes were not significantly different among the types of PTs. No differences were found between patients who underwent a PT at less than 4 months of age and those at greater than 4 months of age. Significantly, however, fecal continence was relatively poor in those less than 15 years of age (50% with only fair to poor continence), but improved markedly once the child reached later adolescence (8%, P < .0002). Correspondingly, the negative impact on the child's social life was much greater in the younger age groups compared with later adolescence (50% of those aged 5 to 15 years v 18% of those > 15 years; P = .007). The effect on the families' lives mirrored this. Finally, only 64% of patients were interpreted as having "normal" stooling habits, yet 90% of parents were moderately or very satisfied with their child's outcome, with no differences found among the three sets of comparison groups. CONCLUSIONS: The outcomes for HD are not always as good as surgeons may perceive; long term follow-up is important. With time, most children significantly improve with respect to fecal continence, but this may not be until later adolescence. In the meantime, the impacts on their social and family lives may be significant. Despite high complication rates, often poor continence, and relative infrequency of normal stooling habits, most parents are satisfied with their child's outcome and adapt to their functional abnormalities along with them.

Adolescent↗
PubMed1999

Characteristics of a highly labile human type 5 17beta-hydroxysteroid dehydrogenase.

17Beta-hydroxysteroid dehydrogenases (17betaHSDs) play an essential role in the formation of active intracellular sex steroids. Six types of 17betaHSD have been described to date, which only share approximately 20% homology. Human type 5 17betaHSD complementary DNA is unique among the 17betaHSDs because it belongs to the aldo-keto reductase family, whereas the others are members of the short chain alcohol dehydrogenases. The characteristics of human type 5 17betaHSD were investigated in human embryonic (293) cells stably transfected with human and mouse type 5 17betaHSD, as well as human type 3 3alphaHSD. Using intact transfected cells, type 5 17betaHSD shows a substrate specificity pattern comparable to those of human type 3 17betaHSD and mouse type 5 17betaHSD. These enzymes catalyze more efficiently the transformation of androstenedione (4-dione) to testosterone, whereas the transformation of dihydrotestosterone to 5alpha-androstane-3alpha,17beta-diol is much lower. In contrast, type 3 3alphaHSD catalyzes more efficiently the transformation of dihydrotestosterone to 5alpha-androstane-3alpha,17beta-diol, whereas the transformation of 4-dione to testosterone represents only 7% of the 3alphaHSD activity. However, upon homogenization, human type 5 17betaHSD activity decreases to approximately 10% of the activity in intact cells and remains stable at this level together with the 3alphaHSD activity. Under the same conditions, however, the mouse enzyme is not altered by homogenization. Indeed, using purified human 17betaHSD overexpressed in Escherichia coli, we could confirm that a much greater amount of protein is required to produce activity similar to the enzymatic activity measured in intact transfected cells. The present data provide the answer to the question of why previous researchers could hardly detect type 5 17betaHSD activity. Indeed, all previous publications used cell or tissue homogenates or purified enzymes. Under such conditions, only the low level, but stable, 3alphaHSD and 17betaHSD activities could be measured, whereas the high level, but highly unstable, 17betaHSD activity could not be measured. As type 5 17betaHSD shares 84%, 86%, and 88% amino acid identity with types 1 and 3 3alphaHSD and 20alphaHSDs, respectively, Northern blot analysis used in previous studies could not provide unequivocal information. In this report, we used a more specific ribonuclease protection assay and could thus show that human type 5 17betaHSD is expressed in the liver, adrenal, and prostate; in prostatic cancer cell lines DU-145 and LNCaP; as well as in bone carcinoma (MG-63) cells. By analogy with type 3 17betaHSD, which is responsible for the formation of androgens in the testis, the expression of type 5 17betaHSD in the prostate and bone cells suggests that this enzyme is involved in the formation of active intracellular androgens in these tissues.

17-Hydroxysteroid Dehydrogenases↗
PubMed1996

Molecular cloning of human type 3 3 alpha-hydroxysteroid dehydrogenase that differs from 20 alpha-hydroxysteroid dehydrogenase by seven amino acids.

We have isolated, by screening a lambda gt11 human prostatic cDNA library, a cDNA clone that shows after transfection into transformed human embryonal kidney (293) cells high 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) activity that catalyzes efficiently the transformation of dihydrotestosterone to 5 alpha-androstane-3 alpha, 17 beta-diol. Chronologically, we name this enzyme type 3 3 alpha-HSD (3 alpha-HSD3). Surprisingly, human 3 alpha-HSD3 shares much higher amino acids sequence identity with human 20 alpha-HSD (97.8%) than with human type 1 and type 2 3 alpha-HSD (81.1 and 85.7% identity, respectively). DNA analysis predicts a protein of 323 amino acids with a molecular mass of 36,844. Alignment of the amino acid sequence of 3 alpha-HSD3 with other related 3 alpha- and 20 alpha-HSDs indicates that 3 alpha-HSD3 shares 68.1, 78.3, and 67.4% identity with rat 3 alpha-HSD and rabbit and rat 20 alpha-HSD, respectively. 3 alpha-HSD3 belongs to the aldo-keto reductase family and like almost all the members of this family preferred NADPH as cofactor.

20-Hydroxysteroid Dehydrogenases↗
PubMed1996

Complications of long-term jejunostomy in children.

The authors reviewed 64 jejunostomies performed in 57 patients. Data were collected regarding complications and performance of the catheters. Patient diagnoses were grouped as follows: cystic fibrosis (25), neurological impairment (14), and miscellaneous other (25). Indications were malnutrition (43), inability to feed (17), and gastroesophageal reflux (4). Complications were compared between these groups. The age range was 7 days to 23 years. There were 251 tube changes over 142 years of cumulative site patency, for an average of 1.8 tube changes per year and an average life of 2.2 +/- 2.4 years per site. The longest duration was 11.7 years. Four tube changes resulted in intraperitoneal insertion (6.2% of changes). The overall complication rate was 37.5%. The major and minor complication rates were 21.9% each. Some patients had more than one complication. Stratification of complications by diagnosis showed that the highest incidence was among the neurologically impaired children (64%), followed by those with cystic fibrosis (32%) and then others (28%). Sixty-four percent of major and 54% of minor complications occurred within the first 6 months. The mortality rate was 4.7%. Infections requiring intravenous antibiotics occurred in 9.4% of the sites, at an average site age of 8.7 +/- 7.7 months. Tube dislodgment requiring surgical replacement occurred in 9.4% of the patients. Our mortality and complication rates compare favorably to those of previously reported series. Surgical jejunostomy is a reliable long-term solution to feeding but is associated with a significant risk of complications, especially in neurologically impaired children. The risk is greatest in the first 6 months after insertion, then decreases as the site "matures."

Adolescent↗
PubMed1996

Human phenol sulfotransferase gene contains two alternative promoters: Structure and expression of the gene.

Phenol sulfotransferases catalyze the transfer of a sulfonate moiety from 3'-phosphoadenosyl 5'-phosphosulfate to a phenolic group of lipophylic substrates to generate soluble sulfate esters. Using a phenol sulfotransferase cDNA as probe to screen a human leukocyte genomic DNA library constructed in lambda EMBL3, we obtained a clone containing a complete gene sequence. Comparison of the gene sequence with that of the corresponding cDNAs, namely phenol-sulfating phenol sulfotransferase (P-PST) or thermostable sulfotransferase (TS-PST), and human aryl sulfotransferase 1 and 2 (HAST1 and HAST2) indicates that the gene possesses eight short exons separated by seven introns included in approximately 5 kb. HAST2 has a different 5' untranslated sequence, and thus is encoded by a different mRNA species. While the nucleotide sequence corresponding to the 5' noncoding region of P-PST (TS-PST and HAST1) is included in the exon I, the 5' untranslated sequence of HAST2 is located in the beginning of exon IIa. The remaining sequence in exon II that is identical to both P-PST and HAST2 was termed exon IIb. Exons III to VIII, which cover the coding region and the 3' untranslated region, are almost identical in all types of PST or AST cDNAs. These results suggest that the phenol sulfotransferase gene possesses two alternate promoters that drive the expression of the two different mRNA species in a tissue-specific manner. Transfection of chloramphenicol acetyl transferase (CAT) reporter gene vectors containing the 5'-flanking sequence upstream from exon I and exon II, respectively, in transformed human embryonal kidney (293) cells indicate that both sequences possess promoter activity with higher activity for promoter 1. RNA blot analysis indicates that human phenol sulfotransferase gene is expressed in kidney, liver, lung, leukocyte, colon, small intestine, and spleen.

Amino Acid Sequence↗
PubMed1995

Inflammatory cloacogenic polyps in children.

Inflammatory cloacogenic polyp (ICP) is a rare lesion arising in the region of the anorectal transitional zone. It is likely caused by occult internal prolapse. Most cases reported in the literature are in the adult population. This is a report of ICP in four children. Awareness of this entity in children is important because of both the propensity for recurrence or persistence of the polyps if the underlying etiology is not corrected, as well as the long-term implications of internal intussusception: procidentia, descending perineum syndrome, and ultimately, incontinence.

Adolescent↗
PubMed1995

Tethered cord with anorectal malformation, sacral anomalies and presacral masses: an under-recognized association.

The association of congenital anal stenosis, scimitar-shaped sacral defect and a presacral mass is known as the Currarino triad. These patients present with constipation of variable severity which may result from a combination of compression by the mass, neurogenic dysfunction as well as anal stenosis itself. We have treated three patients who illustrate the spectrum of severity of this condition. All had an associated tethered cord. One was cured by a single anal dilatation, cord release and anterior meningocele repair. The second did not improve after anoplasty and neurosurgical intervention. A previously diagnosed rectal ectasia was felt to be contributory to the constipation and was treated by low anterior resection with excellent results. The third patient developed an ischiorectal abscess that required drainage and colostomy after unsuccessful dilatation of a very tight and deeply scarred anal stenosis. A subsequent tethered cord release and closure of the anterior meningocele was followed by an anoplasty. Colostomy was closed at a later date. In all patients with anal stenosis a search should be made for a presacral mass and its associated sacral defect. Release of the tethered cord, resection of the presacral mass and/or closure of the anterior meningocele are essential for optimal functional results.

Abnormalities, Multiple↗
PubMed1994

Gastrointestinal mucormycosis causing an acute abdomen in the immunocompromised pediatric patient--three cases.

Mucormycosis is an infection caused by a ubiquitous fungus in immunocompromised individuals. Typically, it invades blood vessels, producing thrombosis and tissue infarction. This infection spans all pediatric age groups and can lead to hollow viscus perforation and bowel obstruction. A 30-month old male with large cell anaplastic lymphoma had a bowel obstruction. During emergency laparotomy, an ileoileal intussusception was identified, which required resection and anastomosis. In the pathological specimen, fungi of the Mucorales order were found to be associated with tissue necrosis. On the eighth day of life, a premature infant had abdominal distension secondary to bowel perforation. Partial gastric resection and multiple intestinal stomas were performed. Death occurred soon after, secondary to multiorgan failure. The autopsy and surgical specimens showed widespread mucormycosis. An adolescent had meningococcemia-induced septic shock. During recovery, hemorrhagic colitis developed, which led to perforation. The subtotal colectomy specimen showed widespread mucormycosis. The laparotomy findings are typical (black necrotic tissue involving the bowel), and when seen in the immunocompromised patient, should make one suspect gastrointestinal mucormycosis. Aggressive surgical debridement of devitalized tissue augmented by intravenous antifungal medication is the mainstay of treatment.

Abdomen, Acute↗
PubMed1993

Fetal tumors associated with hydrops: the role of the pediatric surgeon.

Fetal tumors are being diagnosed with increasing frequency and great accuracy by antenatal ultrasound. High-output cardiac failure and hydrops indicate fetal distress. Management may be limited by the gestational age of the fetus. Our experience with three fetal tumors demonstrates the dilemma with respect to timing of delivery and prognosis. Following the diagnosis of a large sacrococcygeal tumor, a 22-week-gestation fetus became hydropic and died. Another fetus with a rapidly growing posterolateral chest wall mass required cesarean section delivery at 29 weeks gestation. Postnatal course was complicated by pulmonary hypoplasia, intratumoral hemorrhage, and death. The third fetus had an enlarging tumor in the right lobe of the liver. Poor biophysical profile and mild hydrops necessitated cesarean section delivery at 34 weeks. Right hepatic lobectomy was performed and the infant was subsequently discharged home at one month of age. The deleterious effects of the fetal tumor and the need for its removal have to be carefully weighed against the ability of the fetus to survive postnatally.

Adult↗
PubMed1991

The muscle-sparing thoracotomy in infants and children.

Deformities of the chest wall, breast, shoulder girdle, and spine are well-documented sequelae of major thoracotomies that transect muscles, divide major motor nerves, resect ribs, or cause them to fuse. These deformities are probably aggravated by the growth process. This is why we make a plea for the routine use, in infants and children, of a muscle-sparing thoracotomy that will minimize these sequelae without sacrificing exposure. Major (lateral) thoracotomy by this technique involves these steps: (1) creating a transverse incision below the tip of the scapula, or a vertical axillary incision; (2) elevating the skin flaps to expose the muscles; (3) retracting the latissimus dorsi posteriorly; (4) retracting the serratus anterior and scapula superiorly; (5) disinserting the lower origins of the serratus if required only; (6) opening the desired intercostal space; (7) reapproximating the ribs without crowding, using a pericostal suture that is passed along the inferior rib subperiosteally, to avoid any compression on the neurovascular bundle; and (8) allowing the muscles to fall back into place, reattaching the serratus insertions as indicated. Lessened postoperative pain and improved respiratory function are additional benefits.

Child↗
PubMed1991

Gastric volvulus--a late complication of gastrostomy.

Two cases of gastric volvulus are reviewed. Both patients were nonverbal, mentally handicapped children, who were fed through a gastrostomy. They had intermittent intolerance to bolus feeds through the gastrostomy, accompanied by abdominal distension and vomiting of gastric contents. One had a previous partial fundoplication and gastrostomy, and the other had had two pyloroplasties and gastrostomy. The axis of torsion ran from the esophagogastric junction to the gastrostomy site. Both children were treated by detorsion and gastropexy. It is postulated that the gastrostomy served as a fixed point for the volvulus. This was facilitated by the chronically dilated stomachs induced by bolus feeds. These two cases are reported to alert the clinician to this possibility when a neurologically impaired child with a gastrostomy presents with feeding difficulties and persistent vomiting.

Adolescent↗
PubMed1990

Functionalized hydrocarbons with condensed ring skeletons. X. A methyltricyclo[7.4.0.0(2,6)]tetradec-7-ene.

(1) 1,9-trans-1,2-cisoid-2,6-cis-4,11,11-Tris(methoxycarbonyl)-6- methyltricyclo[7.4.0.0(2,6)]-tridec-7-ene-4,2-carbolacton e+ ++, C21H26O8, Mr = 406.43, monoclinic, P1, a = 6.0774 (2), b = 12.3784 (5), c = 14.2565 (4) A, alpha = 72.906 (3), beta = 86.361 (3), gamma = 78.181 (3) degrees, V = 1003.38 (6) A3, Dx = 1.345 Mg m-3, Z = 2, lambda (Cu K alpha) = 1.54056 A, mu = 0.82 mm-1, F(000) = 432, room temperature, final R = 0.043 for 2841 observed reflections. The tricyclic compound (1) has the same carbon framework as in the BCD rings in a steroid nucleus. Ring B adopts a chair while ring C has a half-chair conformation. A trans relative stereochemistry is observed at the BC ring junction while a cis hydrinclane is observed for the CD junction, the lactone bridge being cis to the angular methyl group at C(6) and to the hydrogen at C(1).

Bridged-Ring Compounds↗