Estimated cumulative radiation exposure in patients treated for adolescent idiopathic scoliosis.

PURPOSE: Adolescent idiopoathic scoliosis (AIS) is a progressive spinal deformity, most often observed in female patients of pubescent age. The deformity's severity, its progression through time, its treatment and subsequent follow-up are assessed with routine radiological evaluation of the patient's full spine. This study aimed to determine the cumulative radiation exposure in average patients with AIS treated by brace or surgery throughout their treatment. METHODS: The average number of imaging procedures and corresponding radiation doses were retrospectively obtained from the medical charts of AIS patients treated conservatively and/or surgically at our institution. The median radiation exposure of all imaging modalities was stated in effective dose (mSv). The estimated cumulative effective radiation dose of the each treatment group was determined by multiplication of the average number of imaging conducted, and the median effective radiation dose per imaging modality. RESULTS: In total, 73 AIS patients were included (28 brace, 45 surgically). Patients treated with a brace were subjected to an average of 9.03 full spine radiographs, resulting in an estimated effective cumulative dose of 0.505 mSv over a median treatment period of 3.23 years. Patients treated surgically received an average of 14.29 full spine radiographs over a median treatment period of 2.76 years. The estimated effective cumulative dose amounted from 0.951 to 1.841 mSv, depending on the surgical technique. CONCLUSION: The cumulative effective radiation doses rendered to AIS patients as part of their treatment and follow-up were relatively low. However, every exposure to ionising radiation for medical imaging purposes should be minimised.

Accuracy assessment of pedicle screw insertion with patient specific 3D­printed guides through superimpose CT-analysis in thoracolumbar spinal deformity surgery.

PURPOSE: In order to avoid pedicle screw misplacement in posterior spinal deformity surgery, patient specific 3D­printed guides can be used. An accuracy assessment of pedicle screw insertion can be obtained by superimposing CT-scan images from a preoperative plan over those of the postoperative result. The aim of this study is to report on the accuracy of drill guide assisted pedicle screw placement in thoracolumbar spinal deformity surgery by means of a superimpose CT-analysis. METHODS: Concomitant with the clinical introduction of a new technique for drill guide assisted pedicle screw placement, the accuracy of pedicle screw insertion was analyzed in the first patients treated with this technique by using superimpose CT-analysis. Deviation from the planned ideal intrapedicular screw trajectory was classified according to the Gertzbein scale. RESULTS: Superimpose CT-analysis of 99 pedicle screws in 5 patients was performed. The mean linear deviation was 0.92 mm, the mean angular deviation was 2.92° with respect to the preoperatively planned pedicle screw trajectories. According to the Gertzbein scale, 100% of screws were found to be positioned within the "safe zone". CONCLUSION: The evaluated patient specific 3D-printed guide technology was demonstrated to constitute a safe and accurate tool for precise pedicle screw insertion in spinal deformity surgeries. Superimpose CT-analysis showed a 100% accuracy of pedicle screw placement without any violation of the pedicle wall or other relevant structures. We recommend a superimpose CT-analysis for the first consecutive patients when introducing new technologies into daily clinical practice, such as intraoperative imaging, navigation or robotics.

Peritubular myoid cells are not the migrating population required for testis cord formation in the XY gonad.

Cell migration is one of the earliest events required for development of the testis. Migration occurs only in XY gonads downstream of Sry expression and is required for the subsequent epithelialization of testis cords. Using organ culture experiments and tissue recombination, we and others speculated that peritubular myoid (PTM) cells were among the migratory cells and were likely the cell type required for cord formation. However, because no unique marker was found for PTM cells, their positive identification during or after migration remained unclear. alpha-Smooth Muscle Actin (alphaSma; approved gene symbol Acta2), a classic marker of adult PTM cells,is expressed broadly in testis interstitial cells at E12.5, and becomes highly enriched in PTM cells by E15.5-16.5. We used a novel transgenic line expressingEYFP under the control of an alphaSma promoter to determine whether alphaSma-EYFP positive cellsmigrate into the gonad. Surprisingly, mesonephroi expressing alphaSma-EYFP do not contribute any EYFP positive cells to XY gonads when used as donors in recombination cultures. These results indicate that alphaSma-EYFP cells do not migrate into the gonad during the critical window of sex determination and cannot be the migrating cell type required for testis cord formation. Our results suggest that PTM cells, and most other interstitial lineages, with the exception of endothelial cells, are induced within the gonad. These experiments suggest that endothelial cells are the migrating cell type required for epithelialization of testis cords.

Analysis of cytoskeletal and motility proteins in the sea urchin genome assembly.

The sea urchin embryo is a classical model system for studying the role of the cytoskeleton in such events as fertilization, mitosis, cleavage, cell migration and gastrulation. We have conducted an analysis of gene models derived from the Strongylocentrotus purpuratus genome assembly and have gathered strong evidence for the existence of multiple gene families encoding cytoskeletal proteins and their regulators in sea urchin. While many cytoskeletal genes have been cloned from sea urchin with sequences already existing in public databases, genome analysis reveals a significantly higher degree of diversity within certain gene families. Furthermore, genes are described corresponding to homologs of cytoskeletal proteins not previously documented in sea urchins. To illustrate the varying degree of sequence diversity that exists within cytoskeletal gene families, we conducted an analysis of genes encoding actins, specific actin-binding proteins, myosins, tubulins, kinesins, dyneins, specific microtubule-associated proteins, and intermediate filaments. We conducted ontological analysis of select genes to better understand the relatedness of urchin cytoskeletal genes to those of other deuterostomes. We analyzed developmental expression (EST) data to confirm the existence of select gene models and to understand their differential expression during various stages of early development.

Roles of COX-2 and iNOS in the bony repair of the injured growth plate cartilage.

Growth plate injuries often lead to bone growth defects, which primarily occur due to bony repair at injury sites. Bony repair is preceded by an injury-induced inflammatory response, which could play a role in regulating the repair process. Here, roles of two inflammatory mediators, cyclo-oxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS), in the injury responses were analysed by examining their gene expression and effects of blocking their activities, respectively, with celecoxib and aminoguanidine during 2 days prior to and until 7 days after injury in a rat tibial growth plate injury model. Quantitative RT-PCR assays revealed upregulated expression of COX-2 on days 1 and 4 and iNOS on day 1. Histological analysis of injury sites revealed significant reductions in inflammatory infiltrate (particularly neutrophils) on day 1 in treated groups compared to saline control. While bony tissue proportions at injury sites were unaffected by either treatment, mesenchymal tissue proportions were larger but cartilaginous tissue proportions were smaller on day 8 (though statistically insignificant), and bone remodelling appeared delayed with a smaller bone marrow proportion on day 14 in both treatment groups. These findings suggest that COX-2 and iNOS mediate injury-induced inflammatory response, and may play a role in enhancing mesenchymal cell differentiation to cartilaginous cells and in promoting bone remodelling during bony repair of growth plate injury sites. Furthermore, increased expression of cartilage-related (collagen-2, collagen-10, SOX-9) and bone-related molecules (osteocalcin, cbfalpha-1) suggest involvement of both endochondral and direct bone formation mechanisms during bony repair.

Effects of acute 5-fluorouracil chemotherapy and insulin-like growth factor-I pretreatment on growth plate cartilage and metaphyseal bone in rats.

With the intensified use of chemotherapy and improved survival rates for childhood malignancies, it has become increasingly apparent that some children or adult survivors show poor bone growth and develop osteoporosis. As a step to investigate underlying mechanisms, this project examined short-term effects in rats of chemotherapy agent 5-fluorouracil (5-FU) on cell proliferation, apoptosis, and bone formation at tibial growth plate cartilage and its adjacent bone-forming region metaphysis. In addition, since insulin-like growth factor (IGF-I) is important for bone growth, we examined whether IGF-I pretreatment would potentially protect growth plate cartilage and bone cells from chemotherapy damage. Two days after a single high dose of 5-FU injection, proliferation of growth plate chondrocytes and metaphyseal osteoblasts/preosteoblasts was dramatically suppressed, and apoptosis was induced among osteoblasts and preosteoblasts. As a result, there was a reduction in the chondrocyte number and zonal height at the proliferative zone and a decline in the number of osteoblasts and preosteoblasts on the metaphyseal trabecular bone surface. At day 2, no obvious deleterious effects were observed on the height of the growth plate hypertrophic zone and the bone volume fraction of the metaphyseal primary spongiosa trabeculae. At day 10, while cell proliferation and growth plate structure returned to normal, there were slight decreases in trabecular bone volume, body length increase, and tibial length. While pretreatment with 1-week IGF-I systemic infusion did not attenuate the suppressive effect of 5-FU on proliferation in both growth plate and metaphysis, it significantly diminished apoptotic induction in metaphysis. These results indicate that growth plate cartilage chondrocytes and metaphyseal bone cells are sensitive to chemotherapy drug 5-FU and that IGF-I pretreatment has some anti-apoptotic protective effects on metaphyseal bone osteoblasts and preosteoblasts.

Effect of immediate versus slow intrauterine reduction of congenital diaphragmatic hernia on lung development in the sheep: a morphometric analysis of term pulmonary structure and maturity.

The incidence of congenital diaphragmatic hernia (CDH) is 1:1,200-5, 000, and the condition is associated with high mortality and morbidity attributed principally to associated pulmonary hypoplasia. One treatment approach has been for intrauterine intervention to induce lung growth to a sufficient level to allow survival at birth. Repair of the hernia in utero has been attempted, using a method of immediate reduction and repair of the hernia (patch) compared to a slow reduction method using a silastic "silo" sewn over the diaphragm defect to contain the hernial contents. In animal studies, this second method has been associated with lower fetal morbidity and mortality. This study, utilizing the sheep model of CDH, focuses on analysis of lung structural development and maturation, comparing the efficacy of the immediate vs. slow methods of hernial repair in preventing/reversing pulmonary hypoplasia. We hypothesized that: a) Both the immediate (patch) and slow (silo) methods of hernia repair performed in the lamb model of CDH will stimulate lung growth and structural development and restore lung structure and maturity towards normal levels by term gestation; b) Effects will be detectable by morphometric measurement of the following parameters: lung volume; parenchyma to nonparenchyma tissue ratio; volume density of connective tissue in nonparenchyma; gas exchange tissue to airspace ratio; gas exchange surface area; capillary loading; alveolar/airspace density; and alveolar perimeter; c) Effects will be seen in all lobes of the lung; and d) There will be no significant difference in lung size or structural parameters between the two groups. Forty-four pregnant ewes were allocated randomly to one of four groups. Fetal lambs in three groups (n = 36) underwent CDH creation at days 72-74 of gestation. Of surviving lambs showing an adequate hernia, 9 were not operated on further, 11 underwent "repair" using a silastic chimney around the hernial contents (slow reduction), and 11 underwent "repair" by a silastic patch over the diaphragmatic defect (immediate reduction). The fourth group were normal controls. All surviving lambs (n = 8 in each group) were delivered by Cesarian section at 141-143 days (term = 145-149 days). Lungs were obtained at autopsy, inflation-fixed, divided into lobes, and sampled, and morphometric analysis was performed. Comparisons were made between these groups and with matched normal controls and CDH untreated animals prepared in conjunction and previously reported. The lungs from the CDH animals treated by both methods of fetal hernia repair showed significant lung growth and structural development and maturation, although they remained significantly hypoplastic compared to normal. There were minor differences in the lung parameters between these two groups, with a tendency for the slow method to provide more normal parameter values. An exception was the increase in lung volume that was greater for the immediate (patch) method, particularly in the left lower lobe. In conclusion, intrauterine hernia repair by both methods is capable of partially reversing total lung and lobar structural hypoplasia and immaturity. The slow reduction method, with reduced potential for mortality and morbidity, is at least as good at reversing pulmonary hypoplasia as the immediate method. Alternative intrauterine interventions to prevent or reverse pulmonary hypoplasia are discussed and compared with the hernia repair methods used in this study.

Curve progression and spinal growth in brace treated idiopathic scoliosis.

The risk of progression of idiopathic scoliosis is correlated primarily to factors that predict potential remaining skeletal growth. The aim of the current study was to evaluate spinal growth, measured as the length of the scoliotic spine on serial longitudinal radiographs, and its relationship to progression of the scoliotic curve. The retrospective study was based on measurements made on standing anteroposterior radiographs of 60 patients with adolescent idiopathic scoliosis. In all patients, a Boston brace was prescribed during the followup period. Despite brace treatment, a significantly greater average progression rate of the scoliotic curve was seen in periods of rapid to moderate growth (> or = 10 mm per year) compared with periods of small or no growth (< 10 mm per year). The difference in progression rates concerned the increase of the Cobb angle and the increase of lateral deviation and axial rotation. These findings indicate the length of the spine measured on subsequent radiographs is an excellent parameter to determine spinal growth and thus an excellent predictor of scoliosis progression. With the presented growth charts, which were derived from the measured individual growth velocity values of the patients in the study, it is possible to predict future spinal growth at different chronologic ages.

Morphometric analysis of preterm fetal pulmonary development in the sheep model of congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) in humans carries high mortality/morbidity attributed to associated pulmonary hypoplasia. An understanding of the effects of CDH on fetal lung growth is important for development of successful treatments. This study aimed to quantitate structural differences between normal and CDH-affected preterm lamb lungs. We hypothesized that (a) pulmonary hypoplasia is present in preterm CDH-affected lungs; (b) the relative degree of pulmonary hypoplasia increases with gestation; and (c) the left upper lobe (LUL) is affected most. Fetal lambs were allocated to two groups. One group underwent surgery (72-74 days gestation) inducing CDH. Both groups (n = 7, n = 7) were delivered by cesarean section at 129 days (term: 145-149). Lungs were obtained at autopsy, were inflation-fixed, processed for histology, and morphometry was performed. Preterm lungs of CDH-affected lambs in comparison to those of normal lambs demonstrated a reduction in the following: lung weight (37.7 g vs. 116.3 g); lung weight:body weight (0.012 vs. 0.040); fixed lung volume (33.6 ml vs. 96.9 ml); gas-exchange surface area (4.56 m(2) vs. 13.70 m(2)); parenchyma:nonparenchyma (59:41 vs. 72:28); and parenchymal airspace:tissue (16:84 vs. 35:65). Non-parenchyma connective tissue was increased (58%), airspaces were more numerous (1077/mm(2)) and smaller (perimeter 76.6 microm), gas-exchange surface density (2394 cm(-1)) was greater and capillary loading (0.04 ml/m(2)) was reduced compared to preterm normal lung (49%; 778/mm(2); 108.7 microm; 2003 cm(-1), 0.11 ml/m(2), respectively). The LUL was affected most. These data quantitate pulmonary hypoplasia in preterm CDH-affected lambs. Comparisons with published data indicate increasing relative hypoplasia as gestation proceeds. Fetal interventions will affect lung development, depending on timing, with intervention still likely to be worthwhile during late gestation.

Temporal changes in TFF3 expression and jejunal morphology during methotrexate-induced damage and repair.

Trefoil factor TFF3 has been implicated in intestinal protection and repair. This study investigated the spatiotemporal relationship between TFF3 expression and morphological changes during intestinal damage and repair in a rat model of methotrexate-induced small intestinal mucositis. Intestinal tissues from rats with mucositis were collected daily for 10 days. Mucosal damage was characterized by an initial decrease in cell proliferation resulting in crypt loss, villus atrophy, and depletion of goblet cells, followed by hyperproliferation that lead to crypt and villus regeneration and mucous cell repopulation. TFF3 mRNA levels increased marginally during histological damage, and the cell population expressing TFF3 mRNA expanded from the usual goblet cells to include some nongoblet epithelial cells before goblet cell repopulation. TFF3 peptide, however, was depleted during histological damage and normalized during repair, mirroring the disappearance and repopulation of goblet cells. Although there is no temporal relationship between TFF3 levels and crypt hyperproliferation, confirming the nonmitogenic nature of TFF3, the coincidental normalization of TFF3 peptide with repopulation of goblet cells and mucin production after proliferative overshoot suggests that TFF3 may play a role in the remodeling phase of repair.

A biomechanical analysis of the vertebral and rib deformities in structural scoliosis.

Although the structural changes occurring in the scoliotic spine have been reported as early as the 19th century, the descriptions and biomechanical explanations have not always been complete and consistent. In this study, three-dimensionally rendered CT images of two human skeletons with a scoliotic deformity and two patients with serious scoliosis were used to describe the intrinsic vertebral and rib deformities. The pattern of structural deformities was found to be consistent. Apart from the wedge deformation of the apical vertebrae, a rotation deformity was found in the transversal plane between the vertebral body and the posterior complex: the vertebral body was maximally rotated towards the convexity of the scoliotic curve, whereas the tip of the spinous process was pointed to posterior. The rib deformities at the convex side of the scoliotic curve showed an increased angulation of the rib at the posterior angle, whereas the rib curve on the concave side was flattened. The observed vertebral deformities suggest that these are caused by bone remodelling processes due to forces in the anterior spinal column, which drive the apical vertebral body out of the midline, whereas forces of the musculo-ligamentous structures at the posterior side of the spinal column attempt to minimize the deviations and rotations of the vertebrae. The demonstrated rib deformities suggest an adaptation to forces imposed by the scoliotic spine.

Impact of lifestyle choices on female infertility.

OBJECTIVE: To inform physicians who are involved in the primary care of reproductive-age women of the specific relationships between lifestyle choices and infertility so that they can use this knowledge to educate their patients and encourage changes in behavior. STUDY DESIGN: A review of the relevant literature, performed via Medline search. RESULTS: Prevention of chlamydial and gonorrheal infections; maintenance of the proper body weight; increased individual awareness about the effects of age on fecundity; and reduced intake of caffeine, tobacco and alcohol are all possible avenues for primary prevention of infertility. CONCLUSION: Lifestyle choices can be made that influence the reproductive capability of women. It may be worthwhile for primary care physicians to use information on lifestyle to encourage their patients to improve their overall health while positively affecting their ability to reproduce.

Insulin-like growth factor-I (IGF-I) stimulates regrowth of the damaged intestine in rats, when administered following, but not concurrent with, methotrexate.

BACKGROUND: We tested the ability of insulin-like growth factor-I (IGF-I) to reduce damage to the intestinal mucosa (mucositis) in rats injected with methotrexate. IGF-I was infused concurrent with methotrexate administration and compared to IGF-I administered following the withdrawal of methotrexate. METHODS: Rats were injected with methotrexate at the start of days 1, 2 and 3. IGF-I was infused for 5 days, commencing at the start of day 1 [concurrent administration] or at the start of day 4 [post-methotrexate administration]. RESULTS: IGF-I administered coincident with methotrexate failed to restore mucosal integrity to the damaged small intestine. IGF-I administered post methotrexate stimulated regrowth of the damaged intestine, particularly the ileum, with 22%, 32% and 29% increases in small intestinal weight, ileal villus height and ileal crypt depth respectively. CONCLUSIONS: Following intestinal damage of methotrexate, IGF-I primarily induced growth of the distal small intestine. The ineffectiveness of concurrently administered IGF-I may have represented an IGF-I induced recruitment of proliferating epithelial cells to the anti-proliferative effects of methotrexate.

Methods for reducing energy dissipation in cosmetic gloves.

For cosmetic reasons, hand prostheses are provided with cosmetic gloves. Their pleasing appearance, however, is accompanied by poor mechanical behavior, resulting in a negative influence on prosthesis operation. Glove stiffness is high and nonlinear, and internal friction in the glove material causes energy dissipation (hysteresis). In this article, two methods for reducing hysteresis in cosmetic gloves are proposed, that may be applied independently or in combination. Glove modification. Altering the mechanical properties of the glove itself is the first method that is presented. It was found possible to reduce both stiffness and hysteresis about 50% by forming grooves into the inside of the glove. Together with the evaluation of this method, several properties of the cosmetic glove were determined. Motion optimization. Additionally, a second method for reducing hysteresis was developed. The amount of hysteresis is influenced by the way the glove is forced to deform. The prosthesis mechanism, determining this deformation, was designed for minimum hysteresis and maximum cosmesis. For the prosthesis-glove combination used in this study, thumb motion optimization reduced hysteresis by about 65%.

Effect of antenatal tracheal occlusion on lung development in the sheep model of congenital diaphragmatic hernia: a morphometric analysis of pulmonary structure and maturity.

The incidence of congenital diaphragmatic hernia (CDH) is 1:1,207-5,000, and the condition is associated with high mortality and morbidity, attributed principally to associated pulmonary hypoplasia. Repairing the diaphragmatic defect by antenatal surgery has high mortality, mainly due to premature labor. Antenatal tracheal occlusion, which is achievable by less invasive methods, stimulates lung growth (weight and DNA). However, its effectiveness in reversing structural and maturational abnormalities and its optimal timing requires further investigation. We hypothesized that (1) antenatal tracheal occlusion performed in the lamb model of congenital diaphragmatic hernia will stimulate lung growth and structural development and restore lung structure and maturity toward normal levels by term gestation; (2) effects will be detectable by morphometric measurements of the following parameters: lung volume, ratio of parenchyma to nonparenchyma, volume density of connective tissue within nonparenchyma, ratio of gas exchange tissue to airspace in parenchyma, gas exchange surface area, capillary loading, alveolar/airspace density and alveolar perimeter; (3) effects will be seen in all lobes of the lung; and (4) a greater effect will be observed when tracheal occlusion is performed early rather than late in gestation. Fourteen lambs underwent CDH creation at gestation day 72-74 followed by tracheal occlusion at day 101 (n = 7) or 129 (n = 7). They were delivered by Cesarean section at 143 days (term = 145-149). Lungs were obtained at autopsy, inflation fixed, divided into lobes, and sampled; morphometric analysis was performed. Comparisons were made with previously reported results from control lungs of normal lambs and lambs with untreated CDH. In comparison with untreated lungs, antenatal tracheal occlusion at both times resulted in increased volumes for total lung and lobes, increased volume density of parenchyma and of airspace within parenchyma, and increased gas exchange surface areas. Normal values for gas exchange surface area density, and alveolar density and perimeter were attained and the lungs appeared more mature than non-occluded lungs. Tracheal occlusion earlier in gestation produced a greater effect, achieving greater than normal values for lung volumes and volume densities, whereas the capillary loading value was similar to normal lung. Later occlusion achieved less than normal values for lung volumes and volume densities, with a reduced capillary loading value. We conclude that antenatal tracheal occlusion is capable of reversing structural total lung and lobar hypoplasia and immaturity caused by CDH as determined by morphometrically determined parameters. The effect is greater when tracheal occlusion is performed early rather than late in gestation. The results are encouraging for development of treatment methods for humans with antenatally diagnosed CDH.

Morphometric analysis of pulmonary development in the sheep following creation of fetal diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) in humans is relatively common and associated with high mortality attributed mainly to pulmonary hypoplasia. Previous animal models have induced CDH late in gestation, in contrast to the human situation, and only limited morphometric analyses have been reported. We undertook early surgical creation of CDH in fetal lambs, days 72-74 of gestation (n = 8), with unoperated lambs (n = 8) as controls. At 143 days (term = 145-149) a cesarean section was performed and the lungs were obtained, inflation fixed, divided into lobes, and processed for morphometry. In the CDH group the total lung volumes (51.3 mL compared to 223.8 mL) and gas exchange surface areas (5.85 m2 versus 26.43 m2) were less than one quarter of control values. Capillary loading was reduced from 0.3 mL/m2 in controls to 0.12 mL/m2 in CDH and parenchymal volume reduced from 77% in controls to 57% in CDH. Within parenchyma, gas exchange tissue volume was increased in CDH (66%) compared with controls (50%). CDH lungs had primitive air sacs/alveoli that were smaller (perimeter 83 microns) and more numerous (1321 per mm2) than in controls (perimeter 132 microns, 504 per mm2). The left lung and left upper lobe were affected most. Induction of CDH in the lamb at this early age results in quantifiable, reproducible pulmonary hypoplasia from which comparisons can be made with the human condition.

Glycine as a potential window for minimal access fetal surgery.

Carbon dioxide insufflation of the uterine cavity in sheep enables electrocautery to the surface and superficial tissues of the fetal lamb, using minimally invasive surgery. Absorption of the CO2, however, causes a potentially lethal acidosis. To enable the use of electrocautery dissection of the fetal sheep, without using gas, we have partially replaced the amniotic fluid with 0.5% glycine. To determine whether glycine would have any short- or long-term deleterious effects on the developing fetus, we replaced amniotic fluid with 0.5% glycine in 10 normal fetuses at 101 days of gestation (normal gestation 145-149 days), without later replacing it with the removed amniotic fluid. Histological changes were then sought in the skin, gastrointestinal tract, and pulmonary tree, at 2 ('early', n = 5) or 6 weeks ('late', n = 5) after the introduction of the glycine. There were no histological differences between these and normal sheep at either time point. The use of glycine as a replacement for amniotic fluid subsequently enabled us to carry out electrocautery dissection of the sheep fetus and electrocoagulation of any bleeding vessel. Its use was not associated with any apparent untoward effects. Therefore, it has the potential to be used in minimally invasive surgery on the fetal trachea or on an enlarged fetal bladder.

Milk growth factors enriched from cheese whey ameliorate intestinal damage by methotrexate when administered orally to rats.

Currently, there are no truly effective therapies for the treatment of chemotherapy-induced intestinal mucositis, a debilitating side effect with a pathophysiology common to many chemotherapy regimens. We tested the efficacy of a growth factor extract derived from cheese whey against experimental intestinal mucositis in rats. Rats were subcutaneously injected with the chemotherapeutic drug methotrexate on d 1, 2 and 3 to induce severe damage in the small bowel and bacterial translocation across the gut. Whey extract (15 to 514 mg/d) was given orally for 5-12 d, starting on d 1. Controls were fed an isonitrogenous diet. Histological indices of villus and crypt integrity were utilized to assess potential efficacy of the extract. Administration of the whey extract for 5 d increased the villus surface length indices in the jejunum and ileum by 52% and 56%, respectively (P< 0.001) compared with controls not receiving the whey extract. The crypt area index was 64% greater (P < 0.001) in the jejunum, but not significantly greater in the duodenum or ileum compared with controls not receiving whey extract. Similarly, sucrase activity was significantly higher in the ileum (P < 0.001) but not significantly elevated in the jejunum, whereas bacterial translocation (incidence and number of colonies) was significantly reduced compared with controls not receiving whey extract. We conclude that oral whey growth factor extract reduces methotrexate-induced damage in the small bowel, which suggests clinical applications for the treatment of intestinal mucositis.