Treatment outcomes for hepatoblastoma: an institution's experience over two decades.

Our objective is to review a leading Australian tertiary referral centre's experience in treating hepatoblastoma over two decades. This is a retrospective study of clinical, radiological and pathological data in hepatoblastoma patients treated at our institution between 1984 and 2004. Thirty children (17 male, 13 female) ranging in age from 5 months to 6.5 years (median 19 months) at diagnosis were reviewed. This is the largest case series reported in Australia to date. The median length of follow-up was 6.3 years (range 7 months to 20.9 years). On average, the number of new cases increased by 0.12 each year (P=0.01). A total of 29 patients underwent definitive surgery for primary tumour control. Of these, two (7%) had initial primary surgery, while 27 (93%) had delayed surgery following neo-adjuvant chemotherapy. Chemotherapy regimens included the SIOPEL study protocols. Patients not enrolled in SIOPEL tended to be given more courses of chemotherapy. Ten patients (34%) received an extended right hemi-hepatectomy, six (21%) had right hemi-hepatectomy, seven (24%) had left hemi-hepatectomy, three (10%) had left lateral segmentectomy, and two (7%) had a non-anatomical resection. In addition, two patients required IVC reconstruction at the time of their primary liver resection. Overall survival at 5 years was 89.1% (95% CI 69.8-96.4%). Event-free survival at 5 years was 75.7% (95% CI 53.2-88.5%). There was a clear increase in the risk of recurrence (RR=4.8) and death (RR=4.5) where margins were not microscopically clear. However, neither reached statistical significance in this small cohort. Surgery was still worthwhile even when margins were involved. There was no correlation between mean AFP level at diagnosis, and outcome. Our experience suggests that the achievement of microscopically clear margins at the time of primary tumour resection is an important factor in achieving a positive long-term outcome. In addition, extended courses of neo-adjuvant chemotherapy in patients with pulmonary metastases achieves good long-term outcomes, provided adequate surgical resection of the primary tumour with clear microscopic margins can be achieved.

Estrogen as treatment of hemorrhagic cystitis in children and adolescents undergoing bone marrow transplantation.

Hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (HSCT) can cause significant morbidity and mortality. Previous reports have suggested a role for estrogen in the control of HC in adult patients. Here, we describe the clinical courses of 10 children and adolescents treated with estrogen for HC following HSCT. Eight patients (80%) experienced a significant improvement in their hematuria following the commencement of therapy, with six (60%) undergoing resolution of macroscopic hematuria, without any recurrences. The treatment was well tolerated by the majority of patients, with only one patient needing to interrupt treatment (hepatotoxicity). We conclude that estrogen is well tolerated and often effective, and should be considered as an adjunctive treatment option in children and adolescents with HC following HSCT.

Leukaemia presenting as respiratory distress in a child with asthma.

Asthma is the most common reason for children to present to an emergency department complaining of shortness of breath. The diagnosis, based on one or more of a positive history of atopy, physical examination findings consistent with reactive airways disease, and a clinical response to bronchodilator therapy is usually straightforward. It is important however, to consider other diagnoses, particularly when patients present differently from that which has previously been documented and/or have unexplained physical findings.

Developmental toxicity of di-(C(7)-C(9) alkyl) phthalate and di-(C(9)-C(11) alkyl) phthalate in the rat.

Two phthalate esters, di-(C(7)-C(9) alkyl) phthalate (D79P) and di-(C(9)-C(11) alkyl) phthalate (D911P), have been assessed for their potential to cause developmental toxicity in the rat. Groups of 22 timed-mated Sprague-Dawley rats were administered 250, 500, or 1000 mg/kg D79P or D911P daily by oral gavage (5 ml/kg) between gestation days (GD) 1 and 19. Control animals received the vehicle (olive oil) alone. On GD20, the animals were sacrificed and the fetuses examined. Treatment resulted in no signs of maternal toxicity, as assessed by adjusted maternal bodyweight gain throughout gestation and clinical examinations, and no effects upon litter size, fetal survival or bodyweight. Pups of the high dose D79P and intermediate and high dose D911P groups showed increased incidences of supernumerary lumbar ribs. There was a significant increase in dilated renal pelves in pups of the low dose D79P and high dose D911P groups, but only for D911P was there a significant trend. Consequently, the no observed adverse effect level (NOAEL) for maternal toxicity for both D79P and D911P is 1000 mg/kg/day. The NOAEL values for developmental toxicity are 500 mg/kg/day D79P and 250 mg/kg/day D911P.

Lung transplantation after allogeneic marrow transplantation in pediatric patients: the Memorial Sloan-Kettering experience.

BACKGROUND: Chronic lung disease and pulmonary failure are complications that can occur after bone marrow transplantation (BMT) and are associated with severe morbidity and mortality. METHODS: We report on four patients who developed chronic, progressive, and irreversible lung disease 1 to 3 years after allogeneic BMT in childhood. These patients had chronic graft-versus-host disease (n=3) or radiation-related pulmonary fibrosis (n=1). Three patients underwent double lung transplants and one patient underwent a single lung transplant 2 to 14 years after BMT. RESULTS: All four patients tolerated the lung transplantation procedure well and showed significant clinical improvement with normalization of pulmonary function tests by 1 year posttransplant. One patient died from infectious complications 3 years after lung transplantation, and one patient died after chronic rejection of the transplanted lungs 6 years posttransplant. Two patients remain alive without significant respiratory impairment 2 and 7 years after lung transplantation. CONCLUSION: We conclude that lung transplantation offers a viable therapeutic option for patients who develop respiratory failure secondary to BMT.

Two-generation reproduction toxicity studies of di-(C(7)-C(9) alkyl) phthalate and di-(C(9)-C(11) alkyl) phthalate in the rat.

Di-(C(7)-C(9) alkyl) phthalate (D79P) and di-(C(9)-C(11) alkyl) phthalate (D911P), based on high-normality linear oxo-alcohols, have been assessed for their impact upon reproductive performance in Sprague-Dawley rats. Rats were continuously exposed to either D79P or D911P at dietary levels of 0%, 0.1%, 0.5%, or 1.0% over two generations. Selected F(0) offspring (F(1) generation) were exposed to the same dietary concentration of D79P or D911P as the respective F(0) animals, and were mated to produce F(1) offspring. Both D79P and D911P markedly reduced body weight gain in F(0) and F(1) adult males at the highest dose, but females were affected to a lesser extent. There was no impairment of fertility, fecundity, or development in either generation, but body weights of offspring in the 1.0% D79P and 1.0% D911P groups were slightly and transiently reduced over the weaning period. Although decreases in the weight of several organs were accounted for by depressed body weight, ovary weights were reduced in both generations exposed to 1.0% D79P, and epididymidal weights were slightly reduced in adults of both generations exposed to 1.0% D911P. However, ovarian function-assessed by the oestrus cycle and mating behaviour-and epididymidal sperm concentration, motility, and morphology were unaffected by either substance. Treatment resulted in liver changes, particularly in males, characterised by increased liver weight in young animals, histopathologic changes and reduced organ weight in mature animals, and an increase in palmitoyl CoA oxidase activity. In conclusion, neither D79P nor D911P impaired reproductive function in rats when administered in the diet at levels that induce systemic toxicity, and the NOAEL for effects on reproduction in the rat is 0.5% for both D79P and D911P.

Order of item difficulty on the WAIS-R picture arrangement subtest: data from a traumatically brain-injured sample.

Although the items within the WAIS-R subtests are presumed to be in ascending order of difficulty, several studies have indicated that the Picture Arrangement subtest items are out of order for clinical groups. The present study retrospectively examined item difficulty and discrimination in the test data of 74 individuals who had been referred for neuropsychological assessment following a traumatic brain injury. While results were not statistically significant, qualitative analysis of partial credit scoring for four of the items indicated some inconsistencies in the scoring rationale. Caution is recommended in the use and interpretation of the Picture Arrangement tests scores in the assessment of individuals with traumatic brain injury.

Body condition and the adrenal stress response in captive American kestrel juveniles.

We examined the adrenal response to handling stress of birds in different body conditions. In order to affect the birds' body condition, young (73-d old) female American kestrels (Falco sparverius) were maintained for 6 wk on one of three diets: a control diet (fed ad lib.) and two calorically restricted diets. To invoke a stress response, we removed birds from their cages and took repeated blood samples over the course of an hour. All birds responded to handling stress with an increase in plasma corticosterone, but control birds (in good body condition) showed a more rapid increase to maximum corticosterone levels, followed by a decrease. Both groups of food-restricted birds had a slower rate of increase to maximum corticosterone levels and then maintained high corticosterone levels through 60 min. These results suggest that birds in good physical condition respond more quickly to stressors and adapt physiologically to stressful situations more rapidly than do birds in poor physical condition. This difference may reflect the ability of birds in good condition to mobilize fat for energy, while birds in poor condition must mobilize protein (i.e., muscle).

Real-time visually and haptically accurate surgical simulation.

The Visible Human Database provides a complete submillimeter photographic and radiological description of both a male and a female cadaver. The Center for Human Simulation has developed real-time algorithms that allow a user to wield a virtual scalpel and produce arbitrary cuts into the reconstructed body. Real-time interaction is achieved by producing the appropriate texture mapped surfaces directly from the Visible Human Database. We are currently combining a 3 degree of freedom PHANToM haptic device (SensAble Devices) with our surgical cutting algorithms to produce a system with the look and feel of surgical cutting.

Role of the fetal parathyroid glands and parathyroid hormone-related protein in the regulation of placental transport of calcium, magnesium and inorganic phosphate.

The plasma Ca concentration of the fetus is maintained higher than maternal levels by active placental transport. Ca, Mg and PO4 accumulation by the fetus is mainly associated with skeletal growth. The fetal parathyroid glands are essential for maintenance of elevated plasma Ca, which is necessary for the stimulation of fetal osteoblasts and mineralization of cartilage and osteoid. Fetal thyroparathyroidectomy (TxPTx) results in a decreased activity of the placental Ca pump. The presence of a parathyroid hormone-related protein (PTHrP) has been demonstrated in fetal parathyroid glands and placental tissue. Extracts of fetal parathyroid glands and purified PTHrP, as well as recombinant PTHrP (1-84, 1-108 and 1-141), stimulate Ca and Mg but not PO4 transport across the placenta of TxPTx-ized fetuses perfused with autologous blood in the absence of the fetus. Parathyroid hormone (PTH) and the N-terminal region of PTHrP do not stimulate placental Ca and Mg transport. It is concluded that a mid-molecule region of this novel hormone may be required to stimulate placental Ca transfer and contribute to the regulation of fetal Ca homeostasis.

Does selective attention influence the brain-stem auditory evoked potential?

We have re-examined the problem of selective attention in relation to brain-stem auditory evoked potentials (BAEPs). We compared BAEPs recorded in the relaxed individual with those elicited during visual attention and during auditory attention. Particular emphasis was placed on the use of a demanding visual task to ensure appropriately sustained levels of concentration by the subject for the durations of the tests. We measured the latency of wave I, the wave I-V interval and the amplitudes of waves I and V in 16 subjects in each of the conditions but could find no effect attributable to changes in states of attention. We conclude that there is no evidence for the actions of gating or switching mechanisms at early stages of the auditory pathways.

Stimulation of ovine placental calcium transport by purified natural and recombinant parathyroid hormone-related protein (PTHrP) preparations.

Perfusion in situ of the placenta of previously thyroparathyroidectomized fetal lambs has been used to compare the ability of various forms of parathyroid hormone-related protein (PTHrP) to stimulate placental calcium transport. Whereas PTHrP (1-34) was without effect, PTHrP (1-141) was active but usually after a delay of up to 1 h, in common with the effect noted when using extracts of fetal parathyroid glands. In contrast, PTHrP (1-84) and PTHrP (1-108), tended to show a more rapid stimulatory action. It is suggested that post-translational processing of PTHrP (1-141) may occur as an activating step in the placenta in vivo.

Parathyroid hormone-related protein: isolation, molecular cloning, and mechanism of action.

Many factors, such as interleukin 1, TGF alpha, tumor necrosis factor alpha and beta, and PGs, have been implicated in etiological roles in HHM (Martin and Mundy, 1987). Much interest in the past has also centered upon the likelihood of ectopic secretion of PTH in this condition. We have purified a protein (PTHrP) implicated in HHM from a human lung cancer cell line (BEN). Full-length cDNA clones have been isolated and were found to encode a prepropeptide of 36 amino acids and a mature protein of 141 amino acids. Eight of the first 13 amino acids were identical with human PTH, although antisera directed to the NH2 terminus of PTHrP do not recognize PTH; this homology is not maintained in the remainder of the molecule. PTHrP therefore represents a previously unrecognized hormone, possibly related to the PTH gene by a gene duplication mechanism. In support of this notion, the PTHrP gene has been localized to the short arm of chromosome 12; it is believed that chromosome 11, containing the PTH gene, and chromosome 12 are evolutionarily related. In addition, the human PTHrP gene has been isolated, characterized, and shown to have a similar intron--exon organization as the PTH gene. It is possible that the original ancestral gene is indeed the PTHrP gene; resolution of this question awaits studies in lower species. Peptides synthesized to the predicted protein sequence have enabled detailed structure-function studies that have identified NH 2-terminal sequences to be responsible for the biological effects of the molecule. Antibodies raised against the various synthetic peptides have led to the immunohistochemical localization of PTHrP in many human squamous cell carcinomas as well as in a subpopulation of keratinocytes of normal skin. The availability of these antibodies has opened the way for the development of a radioimmunoassay to detect PTHrP in the sera of cancer patients at risk of developing hypercalcemia. The recent characterization of PTHrP-like activity in the ovine fetus suggests some physiological function for PTHrP. It is possible that PTHrP, as the fetal counterpart of PTH, has the role of maintaining the maternal-fetal calcium gradient. The isolation and characterization of PTHrP have added to our understanding of the mechanisms of hypercalcemia and may contribute to the understanding of other metabolic bone diseases, such as osteoporosis and Paget's disease. Finally, and perhaps most importantly, PTHrP may play a hitherto unrecognized role in normal cell physiology.

Patriarchy, family structure and the exploitation of women's labor.

PIP: The authors present a case for including the patriarchal model into the analysis of female labor force participation in the United States. They argue that only if it is assumed that the division of labor and distribution of goods and services are structured to benefit the male head of the family can various trends be explained, including the low relative income of women compared to men, the increase in female labor force participation without a corresponding increase in household work by men, and the increasing number of divorces initiated by women despite the fact that divorce increases female poverty.^ieng

Evidence for a novel parathyroid hormone-related protein in fetal lamb parathyroid glands and sheep placenta: comparisons with a similar protein implicated in humoral hypercalcaemia of malignancy.

Parathyroid hormone (PTH)-like bioactivity, assayed as adenylate cyclase response in UMR 106-01 osteogenic sarcoma cells, was present in extracts of sheep fetal and maternal parathyroid glands and placenta. Preincubation of extracts with PTH(1-34) antiserum inhibited approximately 40% of the bioactivity in fetal parathyroid extracts, 50% in maternal parathyroid extracts, but only 10% of the bioactivity in the placental extract. Partial purification of placental extracts by chromatography yielded fractions containing PTH-like bioactivity which were similar in behaviour to that of PTH-related protein (PTHrP) from a human lung cancer cell line (BEN). An antiserum against synthetic PTHrP(1-16) partially inhibited the bioactivity of the placental extract and synthetic PTHrP(1-34), but had no effect on the bioactivity of bovine PTH(1-34) or bovine PTH(1-84). The placental PTH-like bioactivity was higher in mid- than in late gestation. Fetal parathyroid glands contained the highest PTH-like bioactivity. Thyroparathyroidectomy of one fetal twin lamb in each of 16 ewes between 110 and 125 days of gestation resulted in decreases of the plasma calcium concentration and reversal of the placental calcium gradient that existed between the ewe and the intact fetus. Perfusion of the placenta of each twin in anaesthetized ewes was carried out sequentially with autologous fetal blood in the absence of the exsanguinated fetus. The plasma calcium concentration in the blood perfusing the placenta of each twin increased, but reached a plateau at a lower concentration in the perfusing blood of thyroparathyroidectomized fetuses than in that of the intact fetuses. Addition of extracts of fetal parathyroid glands or of partially purified PTHrP resulted in further increases in plasma calcium in the autologous blood perfusing the placentae of thyroparathyroidectomized fetuses, but addition of bovine PTH(1-84) or rat PTH(1-34) had no effect. The presence of this PTH-like protein in the fetal parathyroid gland and placenta may contribute to the relative hypercalcaemia of the fetal lamb. This protein, which is similar to PTHrP associated with humoral hypercalcaemia of malignancy, stimulates the placental calcium pump responsible for maintaining a relative fetal hypercalcaemia during gestation.