Effect of steel wire sutures on the incidence of chemically induced rodent colonic tumours

An experiment is presented which shows that colonic primary tumours cluster around a previously constructed anastomosis and that the choice of suture materials (but not the technique of their insertion) can influence this. In a rodent model where dimethylhydrazine was administered 2 months after surgery, anastomotic tumours were most often seen when wire sutures--as used in the staples of anastomotic stapling guns--had been employed (10 out of 16 large bowel tumours were anastomotic as compared with 2 of 12 in a silk sutured group, P = 0.019). An explanation may be that wire sutures persist much longer than silk (in the experiment, 10 months after insertion, 4 per cent of silk sutures were still present, 15 per cent of wire, P less than 0.01). This was translated into a greater degree of scarring at the anastomosis, being most severe in the presence of persisting sutures. Of the 12 anastomotic tumours found in both groups, 7 (58 per cent) were in the minority (17-26 per cent) who had persisting sutures and the remaining 5 in the 47 who had none. Techniques of suturing (needle always passed from the serosa in; needle from mucosa out--the latter in such a way that mucosal cells could be displaced into the bowel wall where it was supposed that they might be more susceptible to subsequent carcinogenesis) did not affect tumour yield. We suggest that non-absorbable sutures, and especially stainless steel wire, should not be used when constructing an anastomosis after large bowel cancer surgery.     

The 1986 McCollum award lecture. Fuel-mediated teratogenesis during early organogenesis: the effects of increased concentrations of glucose, ketones, or somatomedin inhibitor during rat embryo culture

Whole rat embryos were explanted at head-fold, late pre-somite stage (day 9.5 of gestation) and cultured in rat sera varyingly supplemented with glucose (3, 6, 9, or 12 mg/mL), D,L sodium beta-hydroxybutyrate (2, 4, 8, or 16 mM), or both (6 mg/mL D-glucose plus 8 mM beta-hydroxybutyrate). During 48 h culture, increasing glucose alone or beta-hydroxybutyrate alone effected growth retardation and faulty neural and extraneural organogenesis in dose-dependent fashion. Synergistic dysmorphogenic effects occurred when minimally teratogenic concentrations of glucose and beta-hydroxybutyrate were combined. Sera from diabetic animals containing somatomedin inhibitor bioactivity were also able to produce growth retardation and major developmental lesions in presence of amounts of glucose and ketones which of themselves were not teratogenic. Thus, aberrant fuels and fuel-related products can impair growth and organogenesis in early post-implantation embryo. Such fuel-mediated teratogenesis may be multifactorial and include possibilities for synergistic and additive interactions.     

The development of post-traumatic cyst-like lesions in bone

Cyst-like lesions in the radius and tibia were observed in two children as a post-fracture event. The pathogenesis of these lesions is discussed. Cut sections from anatomic specimens display extensive hemorrhage in subperiosteal as well as endosteal and trabecular bone. Cysts arising from hemorrhagic resorption in various locales may explain the occasional atypical appearance of these lesions.     

Comparative metabolism of BHA, BHT and other phenolic antioxidants and its toxicological relevance

Following oral administration, butylated hydroxyanisole (BHA) is absorbed and rapidly excreted by the rat, rabbit and man, with little evidence of long-term tissue storage. The major metabolic pathways for BHA are conjugation (phase 2) reactions, oxidative metabolism (O-demethylation) being relatively unimportant. In the dog, the extent of absorption and urinary excretion is less, and oxidative metabolism is more important than in other species. In contrast, butylated hydroxytoluene (BHT) is cleared less rapidly from most species, enterohepatic circulation being partly responsible for the delay. Tissue accumulation is also greater for BHT than for BHA. Oxidative metabolism (phase 1 reactions) mediated by the microsomal monooxygenase system is the major route for BHT degradation; oxidation of the ring methyl group predominates in the rat, rabbit and monkey, and oxidation of the tert-butyl groups in man. Gallates and 2-tert-butylhydroquinone are mainly metabolized by non-oxidative pathways (methylation or conjugation with sulphate and glucuronic acid). The different biological properties of these compounds may be related to the differences in their absorption and metabolic disposition. Thus, whereas BHT, which is metabolized by oxidation reactions, is an inducer of the microsomal mono-oxygenase system, the other phenolic antioxidants, including BHA, are only weak inducers.     

Effects of Increasing Gestation,Cortisol and Maternal Undernutrition on Hypothalamic Neuropeptide Y Expression in the Sheep Fetus

We have characterized the localization and the ontogenetic changes in Neuropeptide tyrosine (NPY) before birth and investigated the regulation of NPY expression by cortisol and undernutrition in the fetal sheep hypothalamus during late gestation. Using immunohistochemistry, we have identified NPY-containing neurons in the infundibular nucleus and the internal layer of the median eminence in fetal hypothalami collected between 110 and 147 days gestation. NPY projections were also present in the paraventricular nucleus (PVN) of fetal hypothalami at all ages between 110 days gestation and term. There was a significant increase in the amount of immunoreactive NPY/g hypothalamus between 87 and 113 days and 131–140 days gestation and a further significant increase after 141 days gestation. The total hypothalamic content of immunoreactive NPY increased significantly between 87 and 113 days and 141–145 days gestation. The levels of NPY mRNA: 18S rRNA in the mediobasal region of the fetal hypothalamus were significantly higher at 145–146 days gestation than at any earlier gestational age between 116 and 141 days gestation. Cortisol (2.5–3.0 mg/24 h) was infused intrafetally between 109 and 116 days gestation. The ratio of NPY mRNA: 18s rRNA in the mediobasal region of the fetal hypothalamus was significantly higher in the cortisol-infused group when compared with the saline-infused control group at 116 days gestation. Maternal, and hence fetal undernutrition, was induced between 110 and 146 days gestation. At 145–146 days gestation the ratio of NPY mRNA: 18S rRNA in the mediobasal region of the fetal hypothalamus was significantly higher in the undernutrition group when compared with control animals. We have therefore demonstrated that NPY is present in the hypothalamus of the sheep fetus before birth and that hypothalamic NPY content and NPY mRNA increase before delivery. We have also found that glucocorticoids and undernutrition stimulate increases in NPY mRNA levels in the hypothalamus before birth.     

Synthesis and Antitumour Activity of New Derivatives of Flavone-8-acetic Acid (FAA). Part 1: 6-Methyl Derivatives

A range of 17 derivatives of flavone-8-acetic acid (FAA) with a 6-methyl substituent have been prepared and their anti-tumour activity evaluated in vitro against a panel of human and murine tumour cell lines and in vivo against MAC 15A. While many of the compounds show activity comparable to FAA in vitro, this essentially disappears in vivo, possibly due to degradation before the compounds can reach the tumour site.     

Magnetic resonance imaging reveals no ventriculomegaly in polydrug abusers

Previous studies of cerebral structure in substance abusers yielded controversial results, largely due to issues of subject selection and/or limitations of experimental techniques. The purpose of the present study was to assess whether the ventricle-to-brain ratio (VBR), determined volumetrically by magnetic resonance imaging (MRI), differed in polysubstance abusers (n = 10), as compared with age-matched controls (n = 10). Subjects were male volunteers 21–39 years of age. The values of VBR in the polydrug abuse group were not larger than those in control group, nor was there any tendency toward relative ventriculomegaly in the substance abusers. Therefore, the present findings provide no evidence that polysubstance abuse produces abnormalities of gross brain structure in relatively young and physically healthy men.