Epidydimo-orchitis and anorectal malformations: when and in whom?

PURPOSE: Epididymo-orchitis (EO) is infrequently reported in anorectal malformation (ARM) cases. Therefore, it is difficult to assess its risk factors. METHODS: A total of 110 male patients who were operated on for ARM at the same Institution over a period of 13 years were contacted. Association was assessed between EO and the following: spinal dysraphism (SD), symptomatic VUR (VUR), and bowel management (BM) requiring enemas. The data were analyzed with the Chi-square test. RESULTS: A total of 89 patients were contacted. Ten cases of EO were found, and all occurred in patients with recto-urethral (RU) fistula after reconstruction. The patients' age at first episode ranged between 4 and 11 years. RU fistula patients experiencing EO (Group A, 10 patients) were compared with those without EO (Group B, 33 patients). VUR occurred in 9/10 cases in Group A and in 13/33 cases in group B (Chi-square 7.8658, p = 0.005038). SD was present in 4/10 cases in group A and in 13/33 cases in Group B (Chi-square 0.0434, p = 0.83491). A total of 8/10 cases in Group A and 12/33 cases in Group B were on BM (Chi-square 5.87, p = 0.0015). CONCLUSIONS: EO occurs in approximately in 20 % of male cases with ARM, and recto-urinary communication and should be considered the primary diagnosis in the presence of testicular pain. This could avoid unnecessary surgical exploration, and the family should be counseled about this subject.

Short-term neurodevelopmental outcome of babies operated on for low-risk esophageal atresia: a pilot study.

Data on the neurodevelopmental outcome of esophageal atresia (EA) survivors are scarce, controversial, and based on small samples. This is an observational prospective longitudinal study on a selected cohort of low-risk EA survivors. We considered a low-risk EA survivor a patient with the following characteristics: gestational age >32 weeks, no long gap, no genetic or chromosomic anomaly associated with neurodevelopmental delay, and no further major surgical congenital anomalies. Infants were evaluated with scales derived from the Bayley Scales of Infant and Toddler Development - 3rd Edition at 6 and 12 months, with a score of 100 considered normal for each scale. Analysis of variance was used to assess differences of cognitive and motor development. Linear regression was used to assess the impact of the following clinical and sociodemographic variables: gender, birthweight, gestational age, length of hospital stay, number of surgeries and number of esophageal dilatations during first hospitalization, days of mechanical ventilation, weight at follow up, number of surgeries and esophageal dilatations at follow up, parental age, educational level, and socioeconomic status. Thirty children form the object of the study. The mean (standard deviation [SD]) cognitive scale's score was 93.7 (7.5) and 98.2 (9.6) at 6 and 12 months, respectively (P < 0.05). The mean (SD) motor scale's score was 97.6 (9.3) and 98.0 (12.1) at 6 and 12 months, respectively (P = n.s.). Children with a body weight <5° percentile at 12 months showed a mean (SD) cognitive score significantly lower when compared with those with a body weight >5° percentile: 88.8 (6.3) and 100.5 (8.9), respectively. At 12 months, children with unemployed mothers had a mean (SD) motor score significantly lower when compared with those in the other socioeconomic classes: 87.7 (9.8) and 100.6 (12.4), respectively. In conclusion, parents of babies operated on for low-risk EA can be reassured about neurodevelopmental outcome at least up to 1 year of age. When offering a multidisciplinary follow-up program, underweight patients should deserve particular attention to promote their quality of life and support their global development.

Fetal urinoma in females without obstructive uropathy.

OBJECTIVE: Prenatal diagnosis of urinomas has long been established with underlying obstructive uropathy generally responsible for urinary extravasation. Because urinoma formation represents a pop-off mechanism in cases of posterior urethral valves, the number of affected males greatly exceeds the number of females. Fetal urinoma has rarely been reported without obstruction and in females it has only been described as a consequence of a complicated amniocentesis. METHODS: Three cases of fetal urinoma in female fetuses without any dilatation of the urinary tract are described. Since the fetus remained healthy, they were all conservatively managed. RESULTS: Two urinomas resolved after birth and 1 exhibited significant regression. In the second case, a compressed kidney was visualized with fetal MRI. Renal function was impaired in cases 1 and 3 and absent in case 2 (the kidney was no longer visualized). CONCLUSIONS: Fetal urinomas can occur even in the absence of urinary tract obstruction and in a low-pressure system as is found in female fetuses. Fetal MRI may help both visualize the ipsilateral kidney and differentiate the mass from other conditions. In a healthy fetus, fetal urinomas can be conservatively managed, but renal function after birth is often absent or impaired. Whether or not in utero aspiration may be beneficial for the preservation of renal function remains unclear.

Acute oligohydramnios: antenatal expression of VURD syndrome?

OBJECTIVE: Oligohydramnios (OA) is nowadays regarded as one of the best markers of renal function (RF) impairment in bladder outlet obstruction (BOO) detected in utero. As such, its onset is usually early and progressive because of decline in fetal urine production. A series of acute OA complicating pregnancies with BOO has never been reported. METHODS: Over a 7-year period, 5 fetuses with in utero suspicion of BOO exhibited an abrupt decrease of amniotic fluid after the 30th week of gestation. RESULTS: All fetuses were delivered by cesarean section: diagnosis was posterior urethral valves in 3 cases, urethral atresia in 1, and prune-belly syndrome in 1. Urologic work-up demonstrated a unilateral vesicoureteral reflux dysplasia (VURD syndrome) in all 5 fetuses. RF at 1 year was normal in 4 fetuses and impaired in 1. CONCLUSIONS: Besides obstetrical reasons, OA may also have acute onset occurring in the presence of anomalies of the urinary tract; although diagnosis is almost always BOO, functional and anatomical characteristics of the urinary tract are those of VURD syndrome with a non-functioning, refluxing renal unit. The associated acute OA/VURD syndrome may represent a milder expression of a pop-off mechanism advocated in this syndrome with a more favorable prognosis than progressive OA detected early in pregnancy.

A comparison of the effects of daunomycin and adriamycin on various DNA polymerases.

The effects of the anthracycline antiboties, daunomycin and adriamycin, on the DNA-directed activities of DNA polymerases from murine sarcoma virus, rat liver (high-molecular-weight species), Escherichia coli, and Micrococcus luteus were determined. Under all conditions tested, these compounds had greater inhibitory effect against the viral polymerase than against cellular polymerase. The inhibition of murine sarcoma virus DNA polymerase by daunomycin was competitive with respect to DNA. For viral DNA polymerase it was concluded that the inhibition was predominatly caused by the interaction of duanomycin with the primer-template DNA. Also, an appreciable reversal of the daunomycin-induced inhibition of this polymerase by an increase in Mg-2+ concentration is consistent with the conclusion derived by competition experiments. In contrast, the inhibition of both rat liver and M. luteus DNA polymerases was essentially noncompetitive with DNA. Also, bacterial enzymes wer e less sensitive to inhibition by these drugs than the virion polymerase. The strong and preferential inhibiton of viral DNA polymerase is discussed in relation to a differential sensitivity of normal as compared to tumor cells observed in some cell lines.

The interaction of daunorubicin and doxorubicin with DNA and chromatin.

Isotherms that describe the binding of anthracycline antibiotics (including daunorubicin and doxorubicin (adriamycin)) to calf thymus DNA and chromatin have been obtained by means of fluorescence measurements. As expected for charged ligands, the association constants for the interaction of all drugs examined with DNA were found to be dependent on the ionic strength. However, in the case of the daunorubicin-DNA interaction, a marked decrease in the number of binding sites was also observed when the ionic strength was increased. It is suggested that the effect of salt concentration on the number of potential binding sites of daunorubicin molecules to DNA may be the result of some salt-induced alterations in the DNA conformation. This interpretation is also supported by binding data obtained with calf thymus chromatin; Whereas at low salt concentration the binding parameters for the doxorubicin-chromatin interaction are similar to those expected by neutralization of the phosphate groups by histones, modifications of the DNA structure in chromatin are invoked to account for the reduction and heterogeneity of daunorubicin binding sites. The side chain at C-9 could play an important role in determining the strength and specificity of the anthracycline-DNA interaction.

The interaction of adriamycin and its beta anomer with DNA.

The results of thermal denaturation, fluorescence, calorimetric and viscosimetric studies on the interaction of adriamycin and its beta anomer with DNA are reported. Whereas all equilibrium, hydrodynamic and thermodynamic measurements are consistent with the proposed intercalative binding model for the adriamycin-DNA complex, the binding mechanism for the reaction of the beta anomer with DNA remains uncertaian. All DNA binding properties of this stereoisomer are substantially different from those of the parent compound. The results suggest that the amino sugar residue of the natural antibiotic may interact stero-specifically with the DNA helix, thus dictating the orientation of the tetracvclic chromophore within the intercalation site. The alteration in the DNA binding capacity and the changes in interactions with DNA following in inversion of configuration at C-1', parallel a lack of biological activity observed for the beta anomer.

Synthesis, biological and biochemical properties of new anthracyclines modified in the aminosugar moiety.

New 4'-C-methyl analogues of daunorubicin, synthesized by the coupling reaction of daunomycinone with 1-chloroderivatives of protected 4-C-methyldaunosamine analogues, were chemically transformed to the corresponding doxorubicin analogues. Their cytotoxic effect against HeLa cells, ability to bind to DNA, and in vivo toxicity and antitumor activity were compared with those of daunorubicin, doxorubicin, and their 4'-O-methyl analogues. The cytotoxic effect of the new anthracyclines could be correlated with their ability to bind to DNA and with their toxicity in experimental animals; however, the antitumor effectiveness did not seem to be related to these parameters. In general all the compounds retained a remarkable antitumor activity at their optimal doses. The most active compound against P388 leukemia was 4'-O-methyldoxorubicin, which was also more active than doxorubicin against L1210 leukemia.

Molecular structural effects involved in the interaction of anthracyclines with DNA.

Changes in DNA binding ability of daunomycin following structural modifications in the aglycone moiety have been studied by the fluorescence quenching method and by thermal denaturation of the complex. Removal of the methoxyl group at position 4 leads to a slightly stronger binding. Changes in the position of the glycosidic linkage result in a markedly weaker binding. Removal of the hydroxyl group at position 9, with the concomitant formation of a 9,10-anhydro derivative, decreases the binding ability. Methylation of hydroxyl groups at C-6 and C-11 leads to an inactive derivative and makes the binding affinity disappear almost completely. Structure-activity correlations for the DNA binding reaction deduced from these studies are in agreement with earlier findings that relate to the biological activity and confirm the general picture of the binding mechanism.

Changes of activity of daunorubicin, adriamycin and stereoisomers following the introduction or removal of hydroxyl groups in the amino sugar moiety.

The results of a study of the effects of hydroxyl groups at positions, 2, 4 and 6 of the amino sugar on the activity of daunorubicin, adriamycin, and stereoisomers are presented. While the 4'-deoxy derivatives showed a slightly increased biological activity as compared with the parent compounds, the derivatives containing an additional hydroxyl group were less active. It is suggested that the changes in the polarity and in the DNA binding ability of these derivatives are the main factors accounting for the difference in the in vivo activity. The possible relations among the pKa values, the DNA binding properties, and the cellular uptake of the compounds are discussed with particular reference to their therapeutic effectiveness.

Ureteral occlusion prosthesis.

Although temporary or definitive complete ureteral occlusion is rarely needed, there is a considerable number of reports introducing different devices to achieve this goal, most of which can be inserted with minimally invasive procedures. Easy placement is considered of paramount importance, as the candidates are very often in bad general condition as a result of previous surgery, radiotherapy, or other palliative treatments for cancer. A device that can be inserted and removed percutaneously is presented herein. It can be employed in cases of ureteral fistulas resulting from radiotherapy and ureterosigmoidostomy with good results. The technique is simple and not time consuming.

Antenatal diagnosis of surgically correctable anomalies: effects of repeated consultations on parental anxiety.

OBJECTIVE: To assess whether or not a correlation exists between antenatal consultations and parental anxiety. STUDY DESIGN: In total, 31 couples undergoing prenatal consultation after a diagnosis of a surgically correctable anomaly were asked to fill in a questionnaire (Spielberger State-Trait Anxiety Inventory) measuring anxiety levels (AL) both after the first consultation and at birth. Prenatal counselling was done by a perinatal team including paediatric surgeon, obstetrician, and psychologist. RESULTS: Malformations were: eight diaphragmatic hernias, 10 intestinal atresias, four abdominal masses, nine abdominal wall defects. Each fetus was subsequently followed up at regular intervals from diagnosis to birth. AL at birth were then compared with the number of antenatal consultations. A negative correlation (r=-0.688, p<0.001) was found between the number of consultations and the level of anxiety at birth. Patients having at least two consultations had significantly lower anxiety levels at birth. CONCLUSION: Irrespective of the type of malformation, there is evidence that having more than one antenatal consultation may significantly reduce AL at birth. Therefore, early antenatal diagnosis should be encouraged in order to increase as much as possible chances of repeated consultations for the prospective parents.

Physical fitness testing in children operated on for tracheoesophageal fistula.

The maximal physical activity capacity of children operated on for tracheoesophageal fistula (TEF) has not been clearly defined. Eight patients (average age, 12 years) successfully operated on for TEF at birth underwent maximal exercise stress testing on a treadmill, according to the Bruce protocol, to test physical work capacity. Heart rate (HR), oxygen consumption (VO2), and pulmonary ventilation (VE) were measured by a portable lightweight telemetric device. Nine healthy children served as controls. Exercise duration was significantly lower for TEF subjects than for controls (11.6 +/- 1.7 minutes v 15.1 +/- 2.3 minutes; P < .01). Mean HR at rest and during exercise did not differ between the groups. All children reached the maximum HR according to their age; however, for the majority of TEF patients, this occurred at an earlier stage than in the controls. No differences were seen in mean VO2 at rest and on exertion between TEF and control children. However, maximal VO2, as measured at the end of exercise, was significantly different when normalized per kilogram of body weight (VO2/kg = 52.3 +/- 5.8 v 33.3 +/- 6.6; P < .005). The physical rehabilitation of TEF children usually takes into account only respiratory and nutritional factors. However, complete assessment of their cardiac and respiratory function, at rest and on exertion, also should be performed, because this may show that some patients have reduced motor performance; evidence is now accumulating that these children can safely participate in the same physical activities of their healthy peers.

Spinal dysraphism detected by magnetic resonance imaging in patients with anorectal anomalies: incidence and clinical significance.

Though the concept of caudal regression, suggested in 1961 by Duhamel, could explain the association between anorectal anomalies (ARA) and spinal dysraphism (SD), its real incidence may be underestimated and its clinical significance is debatable. From 1988 to 1993, 111 patients with ARA were treated at the authors' institution. Associated anomalies were present in 36% of cases, with the exception of vesicoureteral reflux, which was considered functional rather than anatomical. In view of the late (1 to 2 years after surgical treatment) onset of vesical dysfunction and/or orthopaedic symptoms in some of these patients, a screening protocol was started in 1991, using magnetic resonance imaging (MRI) in all patients with ARA. Fifty patients, 29 boys and 21 girls, underwent a spinal cord MRI, with pathological findings in 25 cases (50%), 13 boys and 12 girls. The authors did not find any significant difference in incidence with respect to high, low, or cloacal malformations. A thickened filum, with or without fibrolipoma, was the most frequent finding, but even tethered cord, syringomyelia, and sac morphological alterations were present. MRI was also able to detect osteoarticular and/or muscular anomalies. Even when a urodynamic study and a neurological and orthopaedic workup were performed in 20 patients undergoing MRI, the clinical significance of these findings remained unclear. However, accurate follow-up of these patients is mandatory in order to detect early neurological symptoms, because currently it is not advisable to refer for neurosurgery all the patients with ARA presenting with anomalies of the spinal cord.

Prenatal diagnosis and clinical outcome of ovarian cysts.

Technical refinements of ultrasound (US) have greatly affected the antenatal diagnosis and treatment of ovarian cysts. From 1985 to 1990 25 consecutive fetuses with ovarian cysts were followed-up by US both during pregnancy and postnatally. All cases were diagnosed between the 28th and 39th weeks of gestation. Deliveries were all at term; cesarean section was required only for obstetric complications. Eight fetuses (32%) showed US patterns of cyst torsion, a finding confirmed at surgery in all. In five patients US patterns suggested complications postnatally that were also confirmed at operation. In six cases cysts increased or remained unchanged in size after 15 days of life: in 50% of these surgery showed ovarian torsion. In the remaining six cases spontaneous resolution occurred within 1 to 4 months. One patient required intrauterine needle aspiration. There were two cases of intestinal obstruction. To date, more than 60% of newborns with ovarian cysts require oophorectomy; however, different treatments (cystectomy, needle aspiration, uncapping) combined with a close US follow-up are likely to reduce this percentage.

Maximal oxygen consumption and stress performance in children operated on for congenital diaphragmatic hernia.

The long-term follow-up of patients operated on for congenital diaphragmatic hernia (CDH) at birth has been extensively evaluated, both clinically and with respect to respiratory function. However, little is known about the sports practice and stress performance of these subjects. Fifteen of 107 patients operated on for CDH underwent exercise stress testing with a stepwise increase in workload. A questionnaire was provided, which requested information on sports practice and lifestyle. Maximal oxygen consumption [Vo2 max] was measured along with dynamic lung volumes. Clinical examination included a whole-body assessment (height, weight, skinfolds) and vital parameters (heart rate and blood pressure). Fifteen healthy children who practiced regular physical activity (2 to 4 hours/week) served as controls. All the CDH patients experienced a good lifestyle, but only 8 of them were participating in sports. Exercise duration and Vo2 max were significantly lower for the CDH patients, and were lowest for the sedentary patients. Therefore, the reduced Vo2 max of these otherwise healthy children most likely represents a lower degree of physical fitness rather than decreased respiratory function. Fitness is an expression of well-being; thus, there is evidence that these patients could safely participate in competitive motor activities.

Stenting for caustic strictures: esophageal replacement replaced.

METHODS: From 1983 to 1996, 31 children with caustic esophageal strictures were seen at Bambino Gesù Children's Hospital; they were all treated conservatively except for two cases complicated by tracheoesophageal fistula. The remaining 29 patients were divided into three groups depending on the treatment, which was modified over the years. Group A (1983 to 1987) consisted of seven patients treated by periodic dilatations; group B (1988 to 1992) consisted of 10 children treated by 40 days of esophageal stenting plus dexamethasone, 0.5 mg/kg/d plus ranitidine plus no oral feeding for 7 to 10 days; group C (1993 to 1996) consisted of 12 cases treated by 40 days of esophageal stenting plus dexamethasone, 1 mg/kg/d plus omeprazole plus early oral feeding resumption. RESULTS: No differences were observed between the three groups of patients with regard to the mean age and to the ingested substance, whereas a significant difference (P = .007) was observed in the mean length of the stricture between group A and C (3.4+/-1.3 and 5.6+/-1.6 cm, respectively). In all but one of the patients (96.5%) complete healing of the stenosis was achieved by conservative treatment, with definitive relief of dysphagia. One patient in group C did not improve after a repeated stenting procedure and was surgically treated. However, in group A, resolution of the stricture was obtained after an average of 19.9+/-14.8 dilatations in a mean period of 25.3+/-17.2 months. In group B, a mean of 12+/-11.3 dilatations were required in a mean period of treatment of 14.1+/-10.6 months. In patients in group C, a mean of 3.5+/-3.2 dilatations were necessary in a mean of 5.8+/-4.8 months. A statistically significant difference was observed both with regard to the number of dilatations and to the duration of treatment, between group A and group C (P = .002) and group B and C (P = .03). CONCLUSION: Esophageal replacement should be considered only in cases complicated by tracheoesophageal fistula or in the rare patients who do not respond to repeated esophageal stenting.

A differential interaction of doxorubicin and daunorubicin with human serum proteins.

The results of a comparative investigation on the interaction of doxorubicin (adriamycin) and daunorubicin with serum proteins are reported. Whereas a strong interaction occurs in vitro between doxorubicin and human serum proteins, no appreciable binding to proteins could be detected for daunorubicin under similar experimental conditions. Since the protein-bound drug is only partially dissociated by physical procedures including gel-electrophoresis, column-chromatography and solvent extraction, the formation of a covalent bond is suggested. The doxorubicin binding to serum proteins is apparently nonselective for a class of proteins; it is strongly reduced in acid conditions and slightly dependent on the ionic strength. Two tentative reaction mechanisms have been considered.

Exteriorization-aspiration minilaparotomy for treatment of neonatal ovarian cysts.

INTRODUCTION: Recent literature indicates that laparoscopic techniques are considered the most appropriate approach for management of neonatal ovarian cysts (NOC). However, laparoscopic equipment may be unavailable in most centers, has high costs, and demands a long learning curve, especially in newborns. METHODS: A minilaparotomy with exteriorization-aspiration ("catch and suck") approach was used in 14 female newborns with antenatally diagnosed ovarian cysts. Average operating time was 25 minutes (range 15-45 min.). Postoperative course was uneventful in all cases; no intra- or postoperative complications were recorded. Length of stay was 48 hours in all patients. CONCLUSIONS: Minilaparotomy with cyst aspiration and subsequent removal may prove a reliable and safe technique in the treatment of NOC: operating time and length of stay are not significantly longer than laparoscopic approach, making this procedure a valid alternative.

Prevalence of hypercontractility in male and female infants with vesico-ureteral reflux.

PURPOSE: To establish whether infants with vesico-ureteral reflux (VUR) have bladder dysfunction, with difference in gender, age at presentation and severity. PATIENTS AND METHODS: 37 infants (24 male and 13 female) aged 2 to 24 months with II degrees to V degrees degree VUR underwent cystometry. Of those, 10 underwent natural filling cystometry. We considered: instability and maximal voiding detrusor pressure (VDP) to be "high" when it exceeded 90 cm H2O. We defined hypercontractility as high VDP and/or instability. RESULTS: The prevalence of hypercontractility was 75% (18/24) in male and 46% (6/13) in female infants (p<0.004). High VDP was found in 50% (12/24) of male and 7% (1/13) of female patients (p < 0.001); no significant difference was found between male (25%) and female ones (38%) with instability alone. The mean VDP was significantly higher in male than in female infants (p < 0.001), in patients < 1 year of age than in older ones (p<0.001) and in severe than in moderate reflux (p<0.006). The mean voiding detrusor pressure of male infants was higher in severe (108+/-46cm H2O) and bilateral (101.3+/-44cm H2O) than in moderate (76+/-24 cm H2O) and unilateral (73.7+/-24 cm H2O) and in infants < 1 year of age (101.7+/-42 cm H2O) than in older ones (70.2+/-21 cm H2O). Natural filling cystometry confirmed the results of standard urodynamic studies. CONCLUSIONS: Bladder dysfunction is confirmed also in infants with reflux, particularly in male younger patients, and it differs in gender. The pathogenesis of congenital reflux is not always a feature of malformation of the vesico-ureteral junction; therefore, patients with bladder dysfunction must be identified early.