Cerebral blood volume measured using near-infrared spectroscopy and radiolabels in the immature lamb brain.

Near-infrared spectroscopy (NIRS) is a technique that is increasingly being used for the noninvasive measurement of cerebral blood volume (CBV) in newborn infants, but it has not been fully validated against established methods. These experiments in immature lambs (gestation 92+/-1 d, mean+/-SEM) compared CBV measured using NIRS-derived estimates of oxygenated Hb (n = 5) with CBV estimated with radiolabeled indicators (125I-labeled serum albumin and 51Cr-labeled red blood cells, n = 10). Total brain CBV (mL/100 g tissue) measured using NIRS was 2.5+/-0.2 compared with 2.5+/-0.2 using radiolabels (NS). Regional tissue plasma, red blood cells, and whole blood volumes from radiolabels varied significantly (p < or = 0.05) throughout the brain. Whole blood volume (mL/100 g tissue) was largest in choroid plexus (16.2+/-2.1) and least in white matter (0.7+/-0.1) with a significant hierarchy evident among regions: choroid plexus > cerebellum > cortex > brain stem = midbrain > white matter. Regional plasma and red blood cell distributions were similar to whole blood, being highest in choroid plexus (13.0+/-1.6 and 3.2+/-0.9, respectively), and least in white matter (0.8+/-0.1 and 0, respectively). These data from the immature lamb brain indicate that total CBV measured with NIRS is essentially identical with the volumes obtained using intravascular radiolabels. Among cerebral regions, white matter contributes little to the global blood volume measured with NIRS because its red blood cell content is very low.

Organ weight/bodyweight ratios: growth rates of fetal organs in the latter half of pregnancy with a simple method for calculating mean organ weights.

Ratios for major organ weights compared with bodyweights of 1023 stillborn and liveborn babies who lived less than 72 h are presented. The ratios were calculated for 2 week increments of gestational age from 20 to 43 weeks and clearly depict the relative growth of fetal organs during the last half of pregnancy. The ratios for heart and for kidneys were virtually constant for the whole period of gestation examined. The ratios for thymus and spleen increased between 20 and 30 weeks gestation and then became constant, although the ratio for the spleen dropped slightly during the last 6 weeks. The ratios for liver, lungs and adrenals decreased between 20 and 30 weeks gestation, and then steadied. The ratio for brain declined very slowly throughout the period examined. An observation of practical importance was that all organ weight/bodyweight ratios were virtually constant after 30 weeks gestation. Approximate mean organ weight/bodyweight ratios between 30 and 43 weeks gestation were: heart 0.007, lungs 0.02, spleen 0.003, liver 0.04, kidneys 0.01, adrenals 0.003, thymus 0.004 and brain 0.13. By multiplying the mean ratio by the total bodyweight, the approximate mean weight for a particular fetal organ can be calculated in situations where charts of normal organ weights are not at hand.

Detection of gonadal carcinoma in situ in childhood and implications for management.

Cells with the characteristic features of carcinoma in situ (CIS) were detected in histological sections of the gonads of three of seven children with clinical syndromes associated with a high risk of gonadal neoplasia. It is suggested that early detection of these cells may be useful in resolving problems of management, including gonadectomy and decisions about sex of rearing. Early detection of CIS cells may have a place in the management of the undescended testis.

Unilateral enlargement of the testis in childhood: does it need exploration?

Unilateral testicular enlargement in the pubertal boy is not an indication for exploration and biopsy, if the clinical features and investigations show no evidence of malignancy. In the prepubertal boy, unilateral testicular enlargement is not necessarily an indication for exploration if there are no clinical or investigational grounds for suspicion of neoplasia. Close follow-up is essential.

Regional cerebral blood flow after hemorrhagic hypotension in the preterm, near-term, and newborn lamb.

Developmental changes in regional cerebral blood flow (CBF) responses to hemorrhagic hypotension during normoxia and normocapnia were determined using radioactively labeled microspheres to measure flow to the cortex, brainstem, cerebellum, white matter, caudate nucleus, and choroid plexus in three groups of chronically catheterized lambs: 90- to 100-d preterm fetal lambs (n = 9); 125- to 136-d near-term fetal lambs (n = 9); and newborn lambs 5- to 35-d-old (n = 8). Heart rate, central venous pressure, and arterial blood pressure were monitored continuously and arterial blood gas tensions, pH, Hb, and oxygen saturation together with regional CBF were measured periodically. Hemorrhagic hypotension produced a mean decrease in arterial blood pressure of 27 +/- 4, 23 +/- 2, and 41 +/- 4% in the three groups, respectively, whereas reinfusion of the lamb's blood resulted in a return to control blood pressure within 3% in all three groups. In the pre-term fetal lamb, CBF decreased significantly in all regions during hypotension. In the near-term fetal lamb, only blood flow to the cortex decreased significantly during hypotension. In the newborn lamb, only the choroid plexus demonstrated a significant decrease in blood flow during hypotension. The lower limit of regional CBF autoregulation was identical to the resting mean arterial pressure in fetal life but significantly lower in newborn lambs. These experiments demonstrate for the first time that vulnerability to hypotension decreases with increasing maturity and that the brainstem, the phylogenetically oldest region of the brain, is the least vulnerable to the effects of hypotension at any age in the lamb model.

Mean organ weights of an Australian population of fetuses and infants.

Charts of organ weights for an Australian population of fetuses and infants are presented. The organ-weight charts were compiled from 1337 stillbirths and liveborn babies whose gestational age ranged from 20 to 43 weeks, and who lived less than 72 h. Macerated stillbirths, multiple births and malformed organs were excluded. Pathological conditions aside from malformations were not excluded, leading to higher standard deviations compared with currently used charts. The organ weights are presented in two-week increments from 20 to 43 weeks' gestation as means, with standard deviations.

Fetal lung growth in laryngeal atresia and tracheal agenesis.

Three cases of airway obstruction in fetuses born at 21, 32 and 40 weeks gestation are reported. The first had laryngeal atresia, cystic dysplastic kidneys, oligohydramnios and immense fluid-filled lungs. The second had upper tracheal agenesis, a tracheo-oesophageal fistula, a cystic dysplastic horseshoe kidney, oligohydramnios and normal-sized lungs. The third had a pin-hole mucosal tract through an otherwise atretic larynx, normal kidneys, no oligohydramnios and normal-sized lungs. Lung weight:body weight ratios, radial alveolar or radial canalicular counts and point-counting of sections of lungs in cases 1 and 2 show that laryngeal or tracheal obstruction may prevent or reduce the pulmonary hypoplasia associated with renal dysplasia, and in cases 2 and 3, that grossly enlarged, hyperplastic lungs may not be seen unless obstruction is complete.

Developmental changes in regional cerebral blood flow in fetal and newborn lambs.

Developmental changes in regional cerebral blood flow (CBF) were determined using radioactively labeled microspheres to measure flow to the cortex, brain stem, cerebellum, white matter, caudate nucleus, and choroid plexus in three groups of chronically catheterized lambs under physiological conditions: 90- to 100-day preterm fetal lambs (n = 14), 125- to 136-day near-term fetal lambs (n = 11), and newborn lambs 5-44 days old (n = 10). We continually monitored heart rate, central venous pressure, and mean arterial blood pressure (MAP) and periodically measured arterial blood O2 and CO2 tensions (PaO2, PaCO2, respectively), pH, hemoglobin, and oxygen saturation (SaO2). The regional CBF measurements (ml.100 g-1.min-1) revealed that in all three age groups the high flow areas are the choroid plexus and caudate nucleus, whereas the lowest flow area is the white matter. There is, however, a different hierarchy of regional CBF in utero (cortex less than cerebellum and brain stem) compared with extrauterine life in the newborn lamb (cortex and cerebellum greater than brain stem). Analysis of regional cerebral oxygen delivery [CBF times arterial oxygen content (CaO2)] demonstrated a progressively increasing oxygen transport to the cortex with increasing gestational maturity and after birth. Oxygen transport to the brain stem, cerebellum, and white matter increased with gestational age, but did not increase after birth. Relationships between regional CBF and natural physiological variations of cardiorespiratory parameters (PaO2, SaO2, CaO2, pH, PaCO2, and MAP) were assessed using regression analysis. Correlations of regional CBF with PaO2 and SaO2 suggest that cerebral perfusion is not primarily determined by CaO2 when variations occur within the physiological range.(ABSTRACT TRUNCATED AT 250 WORDS)

Ultrasound and necropsy study of periventricular haemorrhage in preterm infants.

The diagnostic accuracy of cerebral ultrasound for periventricular haemorrhage was determined by comparing this with necropsy findings in 30 preterm neonates of 30 weeks' gestation or less and birthweight under 1500 g. Ultrasound gave an accurate diagnosis of 85% in infants with germinal layer haemorrhage, 92% in intraventricular haemorrhage, and 97% in intracerebral haemorrhage. False positive errors were caused by vascular congestion; false negative errors occurred when the maximum dimension of haemorrhage was less than 3 mm. Cerebral ultrasound gave a diagnostic accuracy of 63% for periventricular leucomalacia. False negative errors occurred when periventricular leucomalacia was microscopic or when it was out of range of the scanner. The maximum width of the germinal layer was measured in 77 neonates of gestational age 23 to 36 weeks who died and had no periventricular haemorrhage at necropsy. The progressive involution of the germinal layer with increasing gestational age paralleled the steady decrease in incidence of periventricular haemorrhage diagnosed over the same gestational age range. Neonates of the youngest gestational age who had the most extensive germinal layers also had the highest risk for periventricular haemorrhage.

The pathogenesis of renal dysplasia. I. Quantification of hypoplasia and dysplasia.

In order to assess the relative effects of abnormal ureteric orifice position and abnormal urodynamics on the morphogenesis of hypoplasia and dysplasia in kidneys obtained from infants, we devised a method of quantifying the renal structures. The method was based on radial glomerular counts which ranged from zero to normal (seven to nine), a score for dysplastic structures, and the ratio of normal to abnormal tissues present. These three values, when plotted against each other, correlated closely. The glomerular count, with occasional minor adjustment for inconsistencies, was the best parameter of hypodysplasia. Severe to moderate grades of hypodysplasias fell in the low and middle ranges and hypoplasia through to normal in the highest range. By grading kidneys in this way, we were able to compare the effects of ureteral ectopy and abnormal urinary dynamics on the developing kidney.

The pathogenesis of renal dysplasia. III. Complete and incomplete urinary obstruction.

We graded obstructed kidneys of infants on the hypodysplasia scale to assess the influence of complete and partial obstruction on the pathogenesis of hypodysplasia. Kidneys with complete obstruction exhibited severe grades; those with partial ureteral obstruction had near normal grades. Those kidneys subjected to partial urethral obstruction ranged from mild to severe grades which correlated with degrees of lateral ectopy of the urethral office. Renal parenchymal development was impaired by complete obstruction but was tolerant to incomplete obstruction. Abnormal orifice positions associated with urethral obstructions were considered to be manifestations of ectopic ureteric buds and the hypodysplasia to be evidence of abnormal induction of abnormal renal blastema.

The pathogenesis of renal dysplasia. II. The significance of lateral and medial ectopy of the ureteric orifice.

Renal hypoplasia and dysplasia may be primary malformations linked to a panureteric bud deformity or result from damage to the developing nephrons caused by abnormal urodynamic pressures, Kidneys with misplaced ureteric orifices were graded, according to histologic criteria, on the hypodysplasia scale. With lateral ectopy of the ureteric orifices with and without congenital urethral obstruction, the grades correlated with specific orifice positions. The grades of kidneys with caudal ectopy of the ureters indicated a more general correlation. Dysgenesis of the bud and nephrogenic mesenchyme may account for the renal hypodysplasia when the ureteric orifice is found to be ectopic.

Importance of early diagnosis and gonadectomy in 46, XY females.

Gonadal neoplasms developed in three 46, XY females aged 3 yr and 10 mo, 15 yr, and 19 yr. One patient died from metastatic neoplasia. Early diagnosis of 46, XY gonadal dysgenesis is essential, and should be considered in female infants and children with any features of Turner's syndrome, ambiguous genitalia, phallic hypertrophy, excessive height, large hands and feet, failure of development of secondary sexual characteristics, primary amenorrhea, abdominal mass, or unexplained hypertension. Any female with gonadal dysgenesis and a Y chromosome in her karyotype should have prophylactic gonadectomy as soon as possible. The absence of Sertoli cells in these patients, causing lack of androgen binding protein with deficient local concentration of androgens and consequent failure of maturation of spermatogonia, may lead to unregulated proliferation of germ cells, and hence explain the frequency of gonadal neoplasia in the 46, XY female.

Results of the use of autotransplantation of the intraabdominal testis using microsurgical vascular anastomosis.

This study indicates that where facilities are available, the use of autotransplantation of the intraabdominal testis with microsurgical anastomosis to vessels of the groin is an acceptable, and possibly the best, alternative to orchidectomy for the intraabdominal testis. It is certainly justifiable in the case of the bilateral intraabdominal testis but in the case of the unilateral intraabdominal testis with a normally descended and apparently normal testis in the opposite hemiscrotum, the incresed incidence of neoplasia in intraabdominal testes should be taken into account in the decision on the method of treatment.

Normal position of the ureteral orifice in infancy and childhood: a quantitative study.

Normal values for the distance between the vesicoureteral orifice and the internal urethral orifice are given for different ages, heights, weights, crown-to-rump lengths and surface areas of infants and children. A simple estimate of approximate mean values for these measurements also is included.

Germ cells and ova in dysgenetic gonads of a 46-XY female dizygotic twin.

The frequency of germ cell neoplasms in girls with 46-XY gonadal dysgenesis suggests that germ cells may persist in the dysgenetic gonads for many years. A phenotypic female infant with a karyotype of 46-XY in blood, skin, and gonads had a few ova in primordial follicles and numerous germ cells in her dysgenetic gonads at the age of 3 months. At 3 years and 10 months of age her gonads contained no primordial follicle and the only remaining germ cells were in a gonadoblastoma. We propose that germ cells are lost from dysgenetic gonads much more rapidly than from normal gonads, but that the rate of loss in patients with a karyotype of 46-XY may be less than the rate of loss in patients with a karyotype of 45-XO.