Intravesical morphine analgesia is not effective after bladder surgery in children: results of a randomied double-blind study

PURPOSE: Intravesical morphine was recently recommended to reduce postoperative pain after reimplantation surgery for vesicoureteral reflux in children. The efficacy of such treatment, so far solely evaluated by open study, needed to be confirmed. MATERIALS AND METHODS: After parental informed consent was obtained, 80 children requiring Cohen cross-trigonal reimplantation were considered for inclusion in a double-blind study. On the day of surgery patients were randomly assigned to receive either 0.04 mg./kg. morphine per hour or placebo (normal saline) at a constant intravesical infusion rate of 0.08 ml./kg. per hour. Postoperative pain was assessed every 3 hours using a pain score adapted to patient age. If the score was above a predefined limit, patients received intravenous acetaminophen and nalbuphine alternately every 3 hours. Bladder infusion was discontinued after 48 hours. RESULTS: Mean and maximum pain scores as well as the number of scores above the limit were not statistically different when comparing the morphine and placebo groups. There was no difference in the number of doses of analgesics administered. Urine output, voiding frequency and the number of painful voiding episodes were not significantly different between the 2 groups. Plasma morphine concentrations were 3.0 +/- 2.7 and 1.9 +/- 1.9 ng./ml. at 24 and 48 hours in the morphine group and undetectable in the placebo group. CONCLUSIONS: Intravesical administration of morphine is not effective for relieving postoperative pain during the first 48 hours after intravesical ureteral reimplantation. This study emphasizes the importance of controlled studies in evaluating the effectiveness of a new drug or procedure before recommending its use for all patients.     

Response surface methodology for the development of self-nanoemulsified drug delivery system (SNEDDS) of all-trans-retinol acetate

The purpose was to prepare, characterize, and optimize a self-nanoemulsified drug delivery system (SNEDDS) of a model lipophilic compound, all-trans-retinol acetate. As part of the optimization process, the main effects, interaction effects, and quadratic effects of the formulation ingredients were investigated. METHOD: A three-factor, three-level Box-Behnken design was used to explore the quadratic response surfaces and construct a second-order polynomial model in the form: Y = A + A1X1 + A2X2+ A3X3 + A4X1X2 + A5X2X3 + A6X1X3+ A7X1(2) + A8X2(2) + A9X3(2) + E. Amount of added oil (X1), surfactant (X2), and cosurfactant (X3) were selected as the factors. Particle size (Y1), turbidity (Y2), and cumulative amount of the active ingredient emulsified after 10 (Y3) and 30 (Y4) min were the observed variables. Response surface plots were used to demonstrate the effect of factors (X1), (X2), and (X3) on the response (Y4). Amount of added soybean oil (X1), Cremophor EL (X2), and Capmul MCM-C8 (X3) showed a significant effect on the emulsification rates, as well as on the physical properties of the resultant emulsion (particle size and turbidity). Observed and predicted values of Y4 obtained from the constructed equations were in close agreement. Response surface methodology was then used to predict the levels of factors X1, X2, and X3 under the constrained variables for an optimum response. Applied constraints were 0 < Y1 < 0.5, 1 < Y2 < 20, 60 < Y3 < 80, and 90 < Y4 < 100. The predicted values were 0.0704 microm for particle size (Y1), 18.95 NTU for turbidity (Y2), 88.88% for drug release after 10 min (Y3), and 110.7% drug release after 30 min (Y4). Two new formulations were prepared according to the predicted levels. The observed and predicted values were in close agreement.     

The outcome of prenatally diagnosed renal tumors

PURPOSE: We assessed the incidence of perinatal morbidity and evaluated the outcome in children with prenatally diagnosed renal tumors in a retrospective multicenter study. MATERIALS AND METHODS: A review of the records of patients from 20 institutions identified 28 children with prenatally diagnosed renal tumors. Prenatal findings, clinical charts, and radiological, surgical and pathological reports were reviewed in this study. RESULTS: There were 26 congenital mesoblastic nephromas and 2 Wilms tumors. One or more complications were identified in 20 of the 28 cases (71%) during the perinatal period. Polyhydramnios was observed in 11 fetuses (39%), 2 presented with hydrops fetalis and 7 presented in acute fetal distress requiring emergency cesarean section, of which 1 died in utero before delivery. Median gestational age of the 27 neonates born alive was 35 weeks (range 29 to 39), including 13 (46%) who were pre-term (less than 34 weeks of gestation). Complications at birth included hemodynamic instability in 3 newborns, of whom 2 underwent emergency surgery, respiratory distress syndrome in 8 (30%) and hypertension in 6 (22%). Surgical complications occurred in 7 patients (26%), including tumor rupture in 1 and intraoperative bleeding with postoperative death in 1. At a median followup of 42 months (range 2 to 105) 26 of the 27 children were in complete remission. CONCLUSIONS: Fetal renal tumors have an excellent oncological outcome but a high risk of perinatal complications. Prenatal diagnosis should allow planning the delivery at a pediatric tertiary care center to avoid a potentially life threatening condition in neonates in the first hours of life.     

Potential determinant factors of sexual identity in ambiguous genitalia

This is a review of literature scanning the potential factors which may affect Sexual Identity (S.I.) and Gender Identity (G.I.) in patients with ambiguous genitalia. Definitions of these concepts are outlined. Genetic, gonadal, hormonal, social and cultural pressures are reviewed as well as lessons to learn from clinical experiences and outcomes. Current criteriae used to assign gender in a child with ambiguous genitalia are discussed including medical and surgical criteriae as well as cultural disruptors. At the dawn of the third millennium, it is remarkable how little we know about the establishment of our individual and social identities.     

Overexpression of cyclins A and B as markers of neoplastic glandular lesions of the cervix

INTRODUCTION: Cyclins are a family of regulatory proteins that play a pivotal role in controlling the cell cycle. While there is evidence of their altered expression in cervical squamous lesions, their precise role in glandular neoplasia is yet to be elucidated. OBJECTIVES: To investigate the role of cyclins as markers of early cervical glandular neoplasia by comparing their expression in lesions of different histological type. METHODS: Through a cross-sectional analytical study, paraffin wax sections of normal cervix (n = 11), endometriosis/tubo-endometrioid metaplasia (TEM) (n = 19), cervical glandular intraepithelial neoplasia (CGIN) (n = 33), and invasive adenocarcinoma (n = 28) were studied using monoclonal antibodies for cyclins A, B, D, and E with heat pretreatment for antigen unmasking. A quantitative assessment was employed for the analysis of percentage expression of each marker. Statistical analysis of data was performed using SPSS. RESULTS: A progressive significant increase in cyclin A expression occurred from normal cervix (median: 0, IQ: 0-0), through endometriosis/TEM (median: 1, IQ: 0-15) and CGIN (median: 15, IQ: 0-30) to invasive adenocarcinoma (median: 40, IQ: 21.25-60). Cyclin B exhibited a similar pattern (median: 0, IQ: 0-0, median: 0, IQ: 0-0.5, median: 8, IQ: 0.75-15, and median: 30, IQ: 15-45, respectively). Statistically higher expression of cyclin B was found in CGIN than in TEM/endometriosis (P < 0.001). Invasive adenocarcinomas expressed higher levels of cyclins A and B than CGIN (P < 0.001). There was significantly greater cyclin E expression in TEM/endometriosis than in normal cervix (P = 0.03) with a nonsignificant further increase in CGIN and invasive adenocarcinoma. The expression of cyclin D was not significantly different among all groups. CONCLUSIONS: Our data indicate that up-regulation of cyclin A and B expression occurs in neoplastic lesions of the cervix. Cyclin B expression was significantly more widespread in CGIN lesions than in TEM/endometriosis indicating that further assessment of the value of this marker in the diagnosis of cervical glandular neoplasia is warranted.     

Surgical Management of Breast Cancer in Saudi Arabia before and after Outreach Activities

We collected management information from the 1996 referral documents of 100 consecutive patients who came to us for continued treatment of breast cancer. Major deficiencies were noted with regard to clinical assessment, surgery, and pathology. Since 1997 we have intensified our personnel contacts with referring surgeons, and we have performed outreach visits. To measure the effect of our efforts, we repeated the same collection of information between March 2001 and March 2002. Correct performance of TNM (tumor, node metastasis) classification decreased from 36%–16%. The use of mammography increased from 29%–56%, application of fine needle aspiration (FNA) increased from 46%–70%, and use of core needle biopsy (CNB) increased from 0%–6%. The rate of performance of triple assessment (including correct performance of TNM) was 9% and is now 10%. The number of patients who had surgery before referral decreased from 84%–46%. A proper metastatic work-up in the present study was performed in 10% of patients, and mammography was performed in 33% of the patients who had either modified radical mastectomy (MRM) or breast conserving therapy (BCT). Previously, 78 patients had 98 operations before referral and 75% of those needed additional surgery; now only 9 patients out of 39 who had incisional biopsy or lumpectomy needed further surgery. The median number of lymph nodes now is 10, whereas previously 42% of the axillary dissections yielded < 8 lymph nodes. Pathology reports mentioning both tumor size and surgical margins have increased from 29%–53%. These new data indicate that there is a need to join all hospitals in a national guidelines plan for the management of breast cancer.     

Laparoscopic partial adrenalectomy for recurrent pheochromocytoma in a boy with Von Hippel-Lindau disease

We describe a case of a boy with Von Hippel-Lindau disease who presented with recurrent right adrenal pheochromocytoma 4.5 years after laparoscopic bilateral partial adrenalectomy. The boy had a second laparoscopic adrenal-sparing removal of the tumor. By this technique, not only the recurrent tumor was successfully removed but also the unaffected adrenal cortex could be preserved for the second time. To our knowledge, this is the first published case of its type.     

Impact of early screening for reflux in siblings on the detection of renal damage

OBJECTIVE: To assess the impact of screening siblings after detecting significant vesico-ureteric reflux (VUR) and renal scarring, as such screening might identify patients with VUR before urinary tract infections develop, but might also detect clinically insignificant VUR. PATIENTS AND METHODS: We used a previously reported screening protocol to assess the clinical characteristics of patients, including the incidence of renal scarring, and their siblings, and compared the results. In all, 123 children were screened and 44 (36%) had VUR on voiding cystography. The median (range) age at screening was 9 (1-90) months. RESULTS: The grades of VUR detected were < III in 61% and > or = III in 39%; VUR was bilateral in 48%. In all, 37 siblings with VUR were assessed by ultrasonography; 70% were normal, including 12 (32%) children with VUR of grade > or = III. When used, renal scintigraphy was normal in 74% of siblings, vs 18% of index patients. However, when screened after 2 years old, siblings had twice the risk of already having renal damage on renal scintigraphy (P = 0.04). CONCLUSION: Early screening (< or = 2 years) appears to be more protective for avoiding renal damage than screening older patients. Thus we propose early screening in asymptomatic siblings to detect VUR before it becomes clinically significant.