A transgenic insertion causing cryptorchidism in mice.

A distinctive feature of gonadal maturation in mammals is the movement to an extraabdominal location. Testicular descent is a complex, multistage process whereby the embryonic gonads migrate from their initial abdominal position to the scrotum. Failure in this process results in cryptorchidism, a frequent congenital birth defect in humans. We report here a new mouse transgenic insertional mutation, cryptorchidism with white spotting (crsp). Males homozygous for crsp exhibit a high intraabdominal position of the testes, associated with complete sterility. Heterozygous males have a wild-type phenotype, and homozygous females are fertile. Surgically descended testes in crsp/crsp males show normal spermatogenesis. Using FISH and genetic analyses, the transgenic insert causing the crsp mutation has been mapped to the distal part of mouse chromosome 5. Transgene integration resulted in a 550-kb deletion located upstream of the Brca2 gene. A candidate gene encoding a novel G protein-coupled receptor (Great) with an expression pattern suggesting involvement in testicular descent has been identified.

Upper urinary tract manifestations of the VACTERL association.

PURPOSE: In patients suspected to have the vertebral, anal, tracheoesophageal, renal, radial, cardiac and limb abnormalities (VACTERL) association we studied the frequency of upper urinary tract anomalies, prevalence of these features, predictability of upper tract pathology and proper screening evaluation. MATERIALS AND METHODS: From 1991 to 1998 we identified 55 patients with the VACTERL association. Upper urinary tract assessment, including initial renal ultrasound and voiding cystourethrography, and followup data were available for 29 boys and 15 girls. Patients were considered to have the VACTERL association when 3 or more organ systems were involved. RESULTS: Average followup was 5.4 years. Upper urinary tract involvement was noted in 41 of the 44 patients (93.2%) and vesicoureteral reflux in 17 (25 renal units). Of the kidneys 21 were hydronephrotic without reflux or obstruction, 10 were solitary, 3 were multicystic dysplastic, 8 were obstructed and only 17 were normal. A total of 27 patients (61%) underwent at least 1 genitourinary procedure, primarily ureteroneocystotomy. All children were alive at the last followup. CONCLUSIONS: The VACTERL association involves multiple serious anomalies. However, these infants generally have a good outcome. Since the upper urinary system is the most common organ system involved, patients should receive prophylactic antibiotics until an initial urological assessment with renal ultrasound and voiding cystourethrography is performed. It is essential for physicians to know that most children with the VACTERL association have urological involvement that requires treatment and long-term management.

Two cases of fatal air embolism in children undergoing scoliosis surgery.

Venous air embolism during surgery is a rare but important complication and can be rapidly fatal. We present two cases of fatal air embolism in the prone position occurring in small children undergoing surgery for progressive scoliosis. Venous air embolism is a rare complication in the prone position. This is thought to be because in this position there is virtually no gravitational gradient between the site of surgery and the right atrium. The possible sites of entry of air and ways that this may be minimized are discussed.

A renal size nomogram for the patient with myelomeningocele.

PURPOSE: Renal anatomy and function are usually monitored in the myelomeningocele population using routine ultrasound as the child grows. Clinical questions arise when a renal unit is of marginal size when evaluated with nomograms derived from normal patient populations. Our goal was to construct a renal size nomogram using ultrasound for the myelomeningocele population to help the clinician identify abnormal growth. MATERIALS AND METHODS: We reviewed the charts and radiological files of 96 patients with myelomeningocele followed at our institution. Images of 930 renal units were included to construct the nomogram. Patients were excluded from study due to hydronephrosis or hydroureter, solitary kidney, recurrent symptomatic urinary tract infection, vesicoureteral reflux, reconstructive surgery or known high bladder storage pressure. RESULTS: A renal size nomogram was constructed by plotting patient age against maximal renal length on real-time ultrasound. Expected mean and standard deviations were calculated for each age group. CONCLUSIONS: Previous studies using excretory urography have shown that kidneys in the myelomeningocele population are smaller than in a healthy control population. Ultrasound is now the modality most commonly used to monitor renal anatomy. The creation of a renal nomogram based on ultrasound should help the clinician identify abnormal renal growth more accurately.

Androgen receptor gene mutations are rarely associated with isolated penile hypospadias.

PURPOSE: Hypospadias has no known single etiology but it has been linked to androgen insensitivity caused by mutations of the androgen receptor gene. The purpose of this study was to search for such mutations in cases of various degrees of isolated hypospadias to determine whether such an association exists and, if so, with any particular anatomical subgroup. MATERIALS AND METHODS: Isolated deoxyribonucleic acid from the penile tissue of 40 patients undergoing reconstructive surgery was screened for mutations of the coding regions of the androgen receptor gene using single strand conformational polymorphism analysis. In cases with abnormal single strand conformational polymorphism findings sequence analysis of the deoxyribonucleic acid was performed to define the mutation. RESULTS: A missense mutation of exon 2 of the androgen receptor gene was noted in 1 patient with isolated distal penile shaft hypospadias. Sequence analysis revealed that the mutation changed amino acid residue 546 from proline to serine. No abnormalities were detected in the other 39 patients. CONCLUSIONS: Isolated distal shaft hypospadias is associated with mutations of the androgen receptor gene but these mutations appear to be a rare cause of hypospadias.

Effects of surgical skin incision on respiration in patients anaesthetized with enflurane.

We measured ventilation in 12 subjects anaesthetized with enflurane (end-tidal concentration 1.25-1.45%) and nitrous oxide to assess the effect of surgical stimulation on ventilation in humans. Tidal volume and respiratory timing were measured by pneumotachograph before and just after a standardized surgical skin incision. Surgical stimulation increased ventilation by increasing tidal volume, which increased progressively over the first five breaths after incision. The first breath after the stimulus was prolonged, but the timing of the subsequent breaths returned rapidly to the duration observed before incision. Ventilation increased from median 3.6 (quartiles 2.9, 4.3) to 5.4 (3.8, 7.0) litre min-1 (P < 0.01). The increased tidal volume was not associated consistently with shortening of inspiratory duration.