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Site-specific delivery of angiogenic growth factors from tissue-engineered devices should provide an efficient means of stimulating localized vessel recruitment to the cell transplants and would ensure cell survival and function. In the present article, we describe the construction of a novel porous alginate scaffold that incorporates tiny poly (lactic-co-glycolic acid) microspheres capable of controlling the release of angiogenic factors, such as basic fibroblast growth factor (bFGF). The microspheres are an integral part of the solid alginate matrix, and their incorporation does not affect the scaffold porosity or pore size. In vitro, bFGF was released from the porous composite scaffolds in a controlled manner and it was biologically active as assessed by its ability to induce the proliferation of cardiac fibroblasts. The controlled delivery of bFGF from the three-dimensional scaffolds accelerated the matrix vascularization after implantation on the mesenteric membrane in rat peritoneum. The number of penetrating capillaries into the bFGF-releasing scaffolds was nearly fourfold higher than into the control scaffolds (those incorporating microspheric BSA and heparin but not bFGF). At day 10 posttransplantation, capillary density in the composite scaffolds was 45 +/- 3/mm(2) and it increased to 70 +/- 7/mm(2) by day 21. The released bFGF induced the formation of large and matured blood vessels, as judged by the massive layer of mural cells surrounding the endothelial cells. The control over bFGF delivery and localizing its effects to areas of need, may aid in the wider application of bFGF in therapeutic angiogenesis as well as in tissue engineering.

We add two cases of prenatally diagnosed late-onset isolated cystic hygroma to the eight cases reported previously in the English literature. The obstetrical significance, management, and outcome of this entity are reviewed. A retrospective study of late-onset isolated cystic hygromas delivered in one medical centre between 1978 and 1992 was made. The medical records of these newborns served as the basis of the present report. A Medline search of the English literature was carried out. Over a period of 15 years, we observed 11 cases of late-onset congenital isolated cystic hygroma, two of whom had prenatal sonographic diagnosis. In one case, a Caesarean section was performed due to a huge lesion. All cases underwent surgical excision with a favourable outcome. Of the eight prenatally diagnosed cases reported previously, one died at birth due to inability to ventilate and two required a tracheostomy. Late-onset isolated cystic hygroma should be differentiated from the early-onset nuchal cystic hygroma. The differential diagnosis is important, as late-onset isolated cystic hygroma does not require any prenatal intervention, but special awareness during labour and Caesarean section in extreme cases. Transport to a perinatal centre with expert neonatal, respiratory, and paediatric surgical care is recommended. The prognosis in general is favourable.

The present study was undertaken to further explore the comparative dynamics of growth hormone-binding protein (GH-BP) in relation to the turnover of the GH-receptor (GH-R) in vivo in rabbits and rats. The strategy used was to examine the time course of hepatic GH-R turnover over a 3 h period after cycloheximide treatment, with simultaneous measurements of serum GH-BP level. In the rabbit we sampled multiple liver biopsies and serum samples consecutively from each animal. In the rat, experiments on individual animals were conducted for each time point. In the rat, both liver GH-R and serum GH-BP declined after cycloheximide injection following first-order kinetics. The t12 values for GH-R and GH-BP were 29.7–44.5 and 82.7–119.5 min (95% confidence limits), respectively. A significant positive correlation was found between rat liver GH-R and serum GH-BP (r = 0.85; p < 0.001). In contrast, the decline in rabbit liver GH-R, following cycloheximide treatment, was accompanied by simultaneous time-dependent accumulation of serum GH-BP. The t12 for rabbit serum GH-BP accumulation was 30.4–67.6 min. Scatchard analysis of [125I]hGH binding to rabbit GH-BP indicated that the binding capacity increased from 2818 ± 538 fmol/ml, at time zero, to 5236 ± 419 fmol/ml following 60 min cycloheximide treatment (p < 0.05). No significant changes in affinity were observed. Pooling all rabbit data points after cycloheximide injection, a significant negative correlation was found between liver GH-R and serum GH-BP (r = −0.58; p < 0.001). Thus, parallel disappearance of hepatic GH-R and serum GH-BP in the rat following cycloheximide treatment contrasts that in the rabbit, in which the decline in hepatic GH-R was accompanied by simultaneous time-dependent accumulation of serum GH-BP.

The role of the liver in regulating serum growth hormone-binding protein (GH-BP) was studied. We measured rat serum GH-BP and insulin-like growth factor 1 (IGF-1) 30 min to 96 h after 70% partial hepatectomy (PHP) or sham operation in adult male rats. Serum GH-BP declined sharply from 5.8 +/- 0.1% at baseline to 3.9 +/- 0.5% by 48 h following PHP. By 72 h serum GH-BP at baseline to 3.9 +/- 0.5% by 48 h following PHP. By 72 h serum GH-BP returned to baseline level and remained at that level 96 h postoperatively. In sham-operated female rats, serum GH-BP was about 2-fold higher than in males (10.5 +/- 1.46 versus 5.8 +/- 0.2%), whereas 24 h after hepatectomy a significant drop of about 50% was observed (p0.001). Serum IGF-1 decreased within 2-4 h postoperatively in both sham-operated and PHP groups, but thereafter was lower in the PHP rats, up to 48 h after operation, compared to sham-operated rats (p0.03). The study shows that the liver has an important role in the determination of serum GH-BP levels. The return to normal GH-BP level, even before the liver regained its full size following hepatectomy, suggests an increase in GH-BP production by the regenerating liver.

Upper pouch tracheoesophageal fistula (TEF) accompanying esophageal atresia (EA) occurs in less than 1% of all EA/TEF variants and could be easily missed after birth. To confront such diagnostic inaccuracy, perioperative tracheobronchoscopy (TBS) and preoperative upper pouch esophagogram (UPEG) have been proposed but are still controversial. We describe the role of UPEG and TBS, used early after birth, in two cases of EA/TEF with upper pouch TE fistulas with unusual high location (one intrathoracic, one subglotic). These upper TE fistulas were almost missed but ultimately detected very early while employing both UPEG and TBS, wherein UPEG was for the diagnosis of TEF and TBS for both intraoperative diagnostic confirmation and aid in TEF identification. We conclude that UPEG and TBS are complementary in detecting near-missed upper TE fistula accompanying EA. Such approach ensures early and accurate diagnosis of EA/TEF variants, thus preventing the complications of a missed congenital upper pouch TE fistula.

Background Body heat loss during anaesthesia may result in increased morbidity, particularly in high-risk populations such as children. To avoid hypothermia, a novel thermoregulatory system (Allon) was devised. We tested the safety and efficacy of this system in maintaining normothermia in children undergoing routine surgical procedures. Methods The system consists of a computerized body, which receives continuous afferent data, i.e. core (rectal) temperature. These data are then compared with a preset temperature (37 degrees C) and a microprocessor heating/cooling unit warms/cools the temperature of circulating water in a garment that is specially designed to allow maximal coverage of body surface area, without impingement on the surgical field. Water temperature to the garment was limited to a maximum of 39.5 degrees C. Continuous perioperative monitoring of skin and rectal temperature, heart rate and blood pressure was performed. Postoperative shivering and adverse effects were also assessed. Results The Allon system was used in 38 patients aged 3 months to 14 years undergoing surgery under general anaesthesia lasting more than 30 min. Fifty to 80% body surface area was covered by the garment. Mean operative and postoperative core temperatures were 36.9 +/- 0.5 degrees C and 36.7 +/- 0.5 degrees C, respectively. Intraoperative skin temperatures were maintained at 34.4 +/- 2.7 degrees C. The average core- to-periphery intraoperative gradient was 2.9 +/- 4.9 degrees C. Postoperative shivering was absent in 36 cases and mild in two cases. No device-related adverse effects were observed. Conclusions Perioperative thermoregulation using the Allon system is safe and effective in maintaining body temperature within a narrow range in children undergoing brief surgical procedures.

Hepatocyte transplantation is an emerging approach for the treatment of liver diseases. However, broad clinical application of this method has been limited by restricted source of cells and low efficiency of cell integration within the recipient liver. Heparanase cleaves heparan sulfate proteoglycans in the extracellular matrix and basement membrane, activity that affects cellular invasion associated with cancer metastasis and inflammation. This activity has a multifunctional effect on cell-cell interaction, cell adhesion, and angiogenesis. All these factors are important for successful integration of transplanted hepatocytes. Male donor hepatocytes pretreated with heparanase or untreated were transplanted into recipient female rat spleen following partial hepatectomy. Engraftment efficacy was evaluated by PCR for Y chromosome, histology and PCNA, and heparanase immunohistochemistry. In addition, proliferative activity of hepatocytes in vitro was determined by bromodeoxyuridine immunostaining. The number of heparanase-treated cells detected in the recipient liver was significantly increased three- to fivefold within 24-48 h posttransplantation and twofold at 14 days compared with untreated cells. The transplanted hepatocytes treated with heparanase were clearly seen inside portal vein radicles as cell aggregates up to 72 h posttransplantation. The number of portal radicles filled with heparanase-treated hepatocytes was increased compared to control early after transplantation. Heparanase treatment enhanced hepatocyte and sinusoidal endothelial cell proliferation in the liver, and hepatocyte proliferation within the spleen tissue. Preliminary in vitro studies with isolated hepatocytes treated with heparanase showed increased proliferative activity within 24-48 h of cell culture. These results suggest that preincubation of hepatocytes with heparanase increases the presence of hepatocytes within the recipient liver early following cell transplantation and stimulates both hepatocyte and sinusoidal endothelial cell proliferation.