Biomedical subjects

K M Bax

Publications and source records attributed to K M Bax.

10 recordsLinked to original sources

PubMed2000

RET and GDNF gene scanning in Hirschsprung patients using two dual denaturing gel systems.

Hirschsprung disease (HSCR) is a congenital disorder characterised by intestinal obstruction due to an absence of intramural ganglia along variable lengths of the intestine. RET is the major gene involved in HSCR. Mutations in the GDNF gene, and encoding one of the RET ligands, either alone or in combination with RET mutations, can also cause HSCR, as can mutations in four other genes (EDN3, EDNRB, ECE1, and SOX10). The rare mutations in the latter four genes, however, are more or less restricted to HSCR associated with specific phenotypes. We have developed a novel comprehensive mutation detection system to analyse all but three amplicons of the RET and GDNF genes, based on denaturing gradient gel electrophoresis. We make use of two urea-formamide gradients on top of each other, allowing mutation detection over a broad range of melting temperatures. For the three remaining (GC-rich) PCR fragments we use a combination of DGGE and constant denaturing gel electrophoresis (CDGE). These two dual gel systems substantially facilitate mutation scanning of RET and GDNF, and may also serve as a model to develop mutation detection systems for other disease genes. In a screening of 95 HSCR patients, RET mutations were found in nine out of 17 familial cases (53%), all containing long segment HSCR. In 11 of 78 sporadic cases (14%), none had long segment HSCR. Only one GDNF mutation was found, in a sporadic case.

Amino Acid Substitution↗

PubMed1997

Maternoembryonic transfusion and congenital malformations.

There is an increasing number of reports relating chorionic villus sampling (CVS) to transverse limb reduction defects or the oromandibular limb hypogenesis complex. In addition, a correlation has been established between the severity of the defect and the gestational age when CVS is performed. Several hypotheses have been proposed for the increased incidence of congenital malformations after CVS including vascular disruption. Recently, it has been suggested that maternoembryonic transfusion can occur after CVS and that this can lead to a local antibody-mediated reaction, followed by local pathogenetic cell degeneration, i.e., apoptotic cell death, due to vascular disruption. This increased apoptotic cell death will ultimately result in congenital malformations. This paper describes an experimental model that can explain the pathogenesis of congenital malformations after CVS. The model designed uses a whole rat embryo culture technique and intracardiac injection of antisera, mimicking transplacental transfusion after CVS. Injection of antibodies directed against blood group antigens is capable of inducing increased apoptotic cell death. Immunological staining gives evidence of involvement of antibody-mediated reactions in the occurrence of apoptotic cell death. The dorsal aortae in 10-day-old rat embryos of 10-somite stages of development consist of a continuous endothelial cell layer. The effect of intracardiac injection of antisera on the dorsal aortae is only transient. Smaller vessels such as the pharyngeal arch arteries or arteries of the limbs still have fenestrated endothelium and are therefore more vulnerable to the pathogenetic effect of the reaction after transplacental transfusion causing vascular disruption. Development of the vascular pattern and differentiation of the vascular wall reduce the risk of severe malformations later on in pregnancy, although the risk of malformations remains throughout pregnancy. Thus, intracardiac injection of antisera simulating maternoembryonic transfusion such as after CVS can lead to an antibody-mediated reaction with vascular disruption early in pregnancy inducing apoptotic cell death. Increased cell death may ultimately result in congenital malformations, such as transverse limb defects or the oromandibular limb hypogenesis complex.

Animals↗

PubMed1996

Urologic problems in anorectal malformations. Part 2: functional urologic sequelae.

A consecutive series of 90 children with anorectal malformations was reviewed for urologic problems related to lower urinary tract dysfunction. Neurogenic bladder-sphincter dysfunction was seen in 22 patients (24%), all but one of whom had sacral agenesis. Vesicoureteral reflux was present in 60% of the patients with dysfunction, and 32% had reflux nephropathy. Urinary incontinence was present in 91% of the patients who had bladder-sphincter dysfunction. However, the management of bladder-sphincter dysfunction and urinary incontinence was not as straightforward as for patients with myelodysplasia because the parents were more reluctant to accept the therapeutic measures. It was particularly difficult to introduce clean intermittent catheterization (CIC), especially in older patients, because genital and urethral sensation often was undisturbed. Only if CIC had been started in the neonatal period or early infancy were there no problems with acceptance and parental compliance. The authors emphasize the importance of urodynamic testing of neonates and infants who have an anorectal malformation and associated sacral agenesis in identifying those who have neurogenic bladder-sphincter dysfunction. Consequently, patients with lower urinary tract dysfunction should receive prompt treatment, including CIC if necessary, to prevent or reduce secondary urologic morbidity, especially loss of renal function.

Anus, Imperforate↗

PubMed1996

Urologic problems in anorectal malformations. Part 1: Urodynamic findings and significance of sacral anomalies.

A series of 90 children with anorectal malformations received a total of 163 urodynamic studies. The mean number of studies per patient was 1.8 (range, 1 to 7), and the mean age at the time of initial evaluation was 17 months (range, 1 to 128). Sacral anomalies were found in 38 children (42%); 30 of them had partial sacral agenesis and eight had sacral dysplasia without bony defect. Normal lower urinary tract function was found in 98% of the children who had a normal sacrum, in all children who had sacral dysplasia, and in a small number of those who had partial sacral agenesis that affected smaller parts of the S-4 and S-5 pedicles. Severe lower urinary tract dysfunction was observed in 22 patients (24%), all but one of whom had partial sacral agenesis. There was no correlation between the type of sacral agenesis and a specific urodynamic pattern. It is concluded that virtually all children with an anorectal malformation and associated sacral agenesis have neurological bladder-sphincter dysfunction and therefore should receive early urodynamic assessment and appropriate urological treatment.

Abnormalities, Multiple↗

PubMed1996

Prosthetic patches used to close congenital diaphragmatic defects behave well: a long-term follow-up study.

To answer the question of what happens with time with prosthetic patches inserted to close a congenital diaphragmatic hernia, a retrospective study concerning the period 1982-1993 was undertaken. Thirty children received patch reconstruction. None of these patients had agenesis of the diaphragm. Early patch-related complications did not occur, but seven patients died shortly after the operation as a result of lung hypoplasia. Twenty-three patients with patch reconstruction of the diaphragm survived and were followed for a median period of 60 months. Patch-related complications occurred in two: one had a recurrence of the hernia at three months of age, requiring reinsertion of a patch, and one developed a patch abcess at the age of two years, requiring patch removal. Major thoracic wall deformities did not occur, but none of the patients had agenesis of the diaphragm. It is concluded that prosthetic patches used to close congenital diaphragmatic defects behave well.

Abnormalities, Multiple↗

PubMed1995

Laparoscopic approach to surgical management of ovarian cysts in the newborn.

With the improvement of imaging techniques as well as the trend toward routine antenatal ultrasound scanning, the intrauterine diagnosis of fetal ovarian cysts is encountered more frequently. The authors describe the laparoscopic approach to the management of ovarian cysts. This approach is tolerated well by infants, and it may overcome the controversy between conservative and early surgical management by facilitating the subtle transition from diagnostic to therapeutic means, with salvation of the ovary whenever possible.

Female↗

PubMed1995

The effect of posterior sagittal anorectoplasty and its variants on lower urinary tract function in children with anorectal malformations.

The effect of posterior sagittal anorectoplasty (PSARP) and its variants on lower urinary tract function was investigated urodynamically in 32 patients with anorectal malformations. In 27 patients urodynamic evaluation was performed before and after surgery and in 4 it was done postoperatively only. One child was clinically assessed with no postoperative urodynamic study. Minor postoperative changes in the specific preoperative urodynamic pattern were observed in 4 cases but the changes did not seem to be related to surgery. In 3 boys with rectourethral fistulas detrusor failure consistent with autonomic denervation was noted postoperatively. Standard posterior sagittal anorectoplasty was performed in 1 of the 3 boys and posterior sagittal anorectoplasty combined with additional transabdominal procedures was done in the other 2. In general our findings suggest that posterior sagittal anorectoplasty and its variants do not affect lower urinary tract function unless these surgical techniques are combined with major transabdominal procedures and extensive retrovesical dissection.

Anal Canal↗

PubMed1994

Lower urinary tract dysfunction in children with benign sacrococcygeal teratoma.

We evaluated 8 girls and 3 boys with benign sacrococcygeal teratoma for lower urinary tract dysfunction. All children underwent ultrasonography of the urinary tract, voiding cystourethrography and at least 2 standard urodynamic evaluations. Mean patient age at first urodynamic study was 59 months (range 1 to 136). Nine of the 11 children had abnormal studies, including detrusor instability and associated pelvic floor overactivity during micturition in 2, an anatomical infravesical obstruction in 2 and neurogenic bladder-sphincter dysfunction in 5 (2 detrusor hyperreflexia with sphincter dyssynergia, 2 hyporeflexic bladder-sphincter function and 1 detrusor hyporeflexia with normal sphincter function). Although the major cause of neurogenic lower urinary tract dysfunction seems to be related to surgical trauma of the pelvic plexus and sacral nerves, we observed tethered spinal cord as a primary cause in 2 patients. The incidence of voiding dysfunction in children with sacrococcygeal teratoma is high and is usually neurogenic in origin.

Abdominal Neoplasms↗

PubMed1994

Urodynamic evaluation of children with the caudal regression syndrome (caudal dysplasia sequence).

A total of 50 children with the caudal regression syndrome (caudal dysplasia sequence) underwent urodynamic evaluation of lower urinary tract function. Of the patients 15 had isolated sacral agenesis, 13 had sacral agenesis in combination with an anorectal malformation and 22 had an anorectal malformation without sacral anomaly. Neurogenic bladder-sphincter dysfunction was observed in 11 of the 15 children with isolated sacral agenesis (73%) and in 10 of the 13 children with combined sacral agenesis and anorectal malformation (77%). The pattern of neurogenic bladder-sphincter dysfunction in both groups did not differ significantly. In the group of 22 children with isolated anorectal malformation only 1 had signs of neurogenic bladder-sphincter dysfunction. These results indicate that anorectal malformation per se does not influence lower urinary tract function and that the sacral anomaly is the determining factor for neurogenic bladder-sphincter dysfunction in children with anorectal malformation.

Abnormalities, Multiple↗

PubMed1994

Sonography of the coccyx in newborns and infants.

The ultrasonic appearance of the coccyx was studied in 61 newborn infants and young children without known congenital abnormalities. The coccyx was easily seen in all children as a hypoechoic structure with a variable number of vertebral body ossification centers. Knowledge of the normal appearance of the coccyx can prevent confusion with pathologic conditions such as abscesses or tumors and can be helpful in the detection of congenital coccygeal abnormalities.

Cartilage↗