Cancer of the colon in an egg donor: policy repercussions for donor recruitment

This paper describes the tragic case of a young woman who died of cancer of the colon after successfully donating eggs to her younger sister. Although there is no direct link between her operation and the subsequent development of bowel carcinoma, this case imparts a feeling of unease when seen in conjunction with other cases reported during the last few years. It is a reminder that little is known of the long-term consequences of some aspects of assisted conception. Women undergoing ovarian stimulation for themselves or a matched recipient have the right to be advised, in an agreed format, that there is some concern about unproven potential risks from the stimulatory drugs. The safety of egg donors must assume priority over all other considerations, including lack of donors or any moral position. The recent decision by the Human Fertilisation and Embryology Authority (HFEA) to withdraw any form of payment or recompense to egg donors does not seem to us to be based on a balance of scientific advances, patient needs and the ethics of gamete supply. They state that the intention to withdraw payments was implicit in the 1990 Human Fertilisation and Embryology (HFE) Act. However the Act was based on the Warnock report made 6 years earlier. Even in 1990 ovum donation was uncommon and fertility drugs had not yet caused any unease. The Act provided the HFEA with discretionary powers to issue directions so that the future policies would be consistent with any emerging new medical evidence. It is imperative that the HFEA provide convincing evidence on how the current policy of payment to donors harms society, donors or recipients, and how in the UK the new policy will improve medical practice in assisted conception. Successful pilot studies must precede the implementation of any new policy. Failure to do this could cause irreversible harm to the practice of assisted conception using donor gametes, which will ultimately be against the basic aims of the 1990 HFE Act.      

Bovine Colostrum: Its Constituents and Uses

Colostrum is the milk produced during the first few days after birth and contains high levels of immunoglobulins, antimicrobial peptides, and growth factors. Colostrum is important for supporting the growth, development, and immunologic defence of neonates. Colostrum is naturally packaged in a combination that helps prevent its destruction and maintain bioactivity until it reaches more distal gut regions and enables synergistic responses between protective and reparative agents present within it. Bovine colostrum been used for hundreds of years as a traditional or complementary therapy for a wide variety of ailments and in veterinary practice. Partly due to concerns about the side effects of standard Western medicines, there is interest in the use of natural-based products of which colostrum is a prime example. Numerous preclinical and clinical studies have demonstrated therapeutic benefits of bovine colostrum for a wide range of indications, including maintenance of wellbeing, treatment of medical conditions and for animal husbandry. Articles within this Special Issue of Nutrients cover the effects and use bovine colostrum and in this introductory article, we describe the main constituents, quality control and an overview of the use of bovine colostrum in health and disease.     

Effects of Bovine Colostrum with or without Egg on In Vitro Bacterial-Induced Intestinal Damage with Relevance for SIBO and Infectious Diarrhea

Small intestinal bacterial overgrowth (SIBO) occurs commonly, is difficult to treat, and frequently recurs. Bovine colostrum (BC) and chicken eggs contain immunoglobulins and other components that possess antimicrobial, immunoregulatory, and growth factor activities; however, it is not known if they have the ability to reduce injury caused by the presence of bacteria associated with SIBO (Streptococcus, Escherichia coli, Staphylococcus, Bacteroides, Klebsiella, Enterococcus, and Proteus) and infectious diarrhea (enteropathogenic Escherichia coli, Salmonella). We examined the effects of BC, egg, or the combination, on bacterial growth and bacteria-induced changes in transepithelial electrical resistance (TEER) and bacterial translocation across confluent Caco-2 monolayers. BC, egg, or the combination did not affect bacterial growth. Adding bacteria to monolayers reduced TEER and (with minor variations among species) increased bacterial translocation, increased monolayer apoptosis (increased caspase-3 and Baxα, reduced Bcl2), increased intercellular adhesion molecule 1 (ICAM-1), and reduced cell adhesion molecules zonulin1 (ZO1) and claudin-1. BC, egg, or the combination reduced these effects (all p < 0.01) and caused additional increases in vascular endothelial growth factor (VEGF) and Heat Shock Protein 70 (Hsp70) expression. We conclude that BC ± egg strengthens mucosal integrity against a battery of bacteria relevant for SIBO and for infectious diarrhea. Oral BC ± egg may have clinical value for these conditions, especially SIBO where eradication of precipitating organisms may be difficult to achieve.     

Investigation of three new mouse mammary tumor cell lines as models for transforming growth factor (TGF)-β and Neu pathway signaling studies: identification of a novel model for TGF-β-induced epithelial-to-mesenchymal transition

Introduction  

This report describes the isolation and characterization of three new murine mammary epithelial cell lines derived from mammary tumors from MMTV (mouse mammary tumor virus)/activated Neu + TβRII-AS (transforming growth factor [TGF]-β type II receptor antisense RNA) bigenic mice (BRI-JM01 and BRI-JM05 cell lines) and MMTV/activated Neu transgenic mice (BRI-JM04 cell line).     

Response to influenza virus vaccination in vertical HIV infection

OBJECTIVE: To assess the antibody response to influenza vaccine of children vertically infected with HIV. DESIGN: Prospective study in HIV infected children vaccinated during the winter of 1994-5. SETTING: Family HIV clinic at St Mary's Hospital, Paddington. SUBJECTS: 25 children, aged 1-11 years, vertically infected with HIV. MAIN OUTCOME MEASURES: Responses to influenza antigens (H1N1-A/Taiwan/1/86, H3N2-A/Shandong/9/93, B/Panama/45/ 90) were tested by haemagglutination inhibition. Antibody responses were assessed according to clinical symptoms and immune function, stratified according to the 1994 revised classification for HIV infection in children. RESULTS: 23 children (92%) had either very low or no detectable antibody before vaccination. New protective antibody responses were made by 10 children (40%): in seven to a single antigen, in two to two antigens, and in one to all three antigens. For each antigen there was an overall small increase in the mean geometric titre of antibody produced, but this only reached a protective level for antigen H1N1 and for children with minimal symptoms. Less symptomatic children were significantly more likely to produce a protective antibody response to influenza vaccination. No association was found between immune function, as measured by CD4 count, and vaccine response. CONCLUSIONS: Only vaccination of the least symptomatic HIV infected children against influenza is likely to be effective. This will not only protect them against influenza, but will also protect other more immunosuppressed and vulnerable members of their families.     

"Early-peak" carbon monoxide production in certain erythropoietic disorders

The "early-labeled" peak (ELP) of 14CO excretion following injection of glycine-2-14C was used to study erythropoiesis in a patient with sideroblastic anemia and in four subjects with myeloproliferative disorders. The ELP was greatly enlarged in all patients, as compared with a normal volunteer. The contour of the peaks from the hematologically abnormal subjects suggested the presence of increased erythroid heme degradation. In the patient with sideroblastic anemia, all hours of the early peak were significantly reduced after transfusion. This was interpreted to mean that even the earliest or "nonerythroid" phase of the peak is influenced by erythropoietic activity, at least under conditions of erythropoietic stress.     

pH-dependent secretion of gastrin in duodenal ulcer disease: effect of suppressing Helicobacter pylori.

Patients with duodenal ulcers and Helicobacter pylori infection have elevated plasma gastrin concentrations which fall after suppression of the organism. This may be due to H. pylori elevating the pH of the antral mucous layer, therefore preventing luminal acid from inhibiting gastrin release. To test this idea, we measured the plasma gastrin concentrations under basal conditions and in response to 4% peptone when the gastric lumen was maintained at pH 2.5 and at pH 5.5 by gastric perfusion. We studied 11 duodenal ulcer patients before and after suppression of H. pylori. Gastrin concentrations were significantly higher before suppression of H. pylori than after treatment in all three states; basal gastrin (pmol/l) fell from 9.2 (3.7-23, median and range) to 5.1 (1.7-15) after treatment; from 11.3 (3.8-29) to 5.9 (5.7-6.1) at pH 2.5 and from 15.2 (3.9-32) to 7.15 (6.1-14) at pH 5.5. The ratio of peptone-stimulated gastrin at pH 2.5/pH 5.5 was similar before (0.8; 0.5-1.7) and after (0.8; 0.5-1.1) suppression of H. pylori. These results indicate that infection with H. pylori increases basal and peptone-stimulated plasma gastrin concentrations, and that this response is independent of luminal pH.     

Dose-dependent effects of fentanyl on indomethacin-induced gastric damage.

Whilst developing a rat model for studies of gastric protection, we noticed that the anaesthetic agent 'Hypnorm', containing the opiate fentanyl 0.315 mg/ml and the butyrophenone fluanisone 10 mg/ml, was itself protective against indomethacin-induced damage: unrestrained animals given indomethacin (20 mg/kg) subcutaneously had an ulcer score of 9 +/- 1 mm2, compared with 1 +/- 1 mm2 in animals pre-treated with Hypnorm (0.8 ml/kg) and then given indomethacin (p less than 0.01). Further investigation showed this effect to be due to fentanyl-inhibiting gastric acid secretion: doses of fentanyl (90 and 180 micrograms/kg) which decreased indomethacin-induced damage also caused a rise in intragastric pH from 2.7 +/- 0.6 in controls to 5.1 +/- 0.8 and 5.0 +/- 0.8, respectively. However, the response of fentanyl varied depending on the dose given: fentanyl, 3.6 micrograms/kg did not affect indomethacin-induced damage, 8 +/- 2 vs. 9 +/- 1 mm2; fentanyl, 18 micrograms/kg potentiated damage, 15 +/- 4 mm2 (p less than 0.05), whereas fentanyl, 90 micrograms/kg and 180 micrograms/kg decreased damage, 2 +/- 1 mm2 and 0.1 +/- 0.1 mm2, respectively (p less than 0.01). Neither the butyrophenone haloperidol (8.3 mg/kg) nor the alpha-adrenergic receptor antagonist phenoxybenzamine (3 mg/kg) protected against indomethacin-induced damage. We conclude that fentanyl affects intragastric pH and can both potentiate and protect against indomethacin-induced damage. Furthermore, the potentiation of gastric damage by fentanyl occurred at doses similar to those used for human anesthesia, so clinical studies are suggested.