Reactions to Gudair® vaccination identified in sheep used for biomedical research.

CASE REPORT: We report Gudair® vaccination (against ovine Johne's disease, Mycobacterium avium subsp. paratuberculosis) site reactions in sheep used as a surgical model in biomedical research and discuss the actual and potential impact these lesions may have on surgical procedures, particularly in otology. Nine female Merino-cross sheep (Ovis aries) were enrolled in a project designed to investigate the healing capabilities of the malleus bone in the middle ear. The sheep were 12-18 months of age. Eight sheep had lesions near the base of the right ear that were discovered when surgery was performed. The size of the lesions varied and all lesions had a thick capsule containing various amount of caseous material. Two lesions had a draining tract where purulent material was apparent at the lowest point. The prescapular lymph nodes were not palpable in any of the sheep. Aerobic growth of various organisms was reported from four sheep lesions when the purulent material was transferred to a broth media. Histopathological examination revealed intralesional Mycobacteria and focal caseous necrosis or granulomatous dermatitis and cellulitis in seven of the eight lesions. Mild necrotising to granulomatous dermatitis and cellulitis was described in the lesion where organisms were not found. CONCLUSIONS: The lesions were confirmed at the end of the study to be associated with the vaccination and did not cause any known adverse effects on the research. However, it is important to acknowledge the risk of contamination these lesions could have on a sterile surgical site.

Prenatal cytokine exposure results in obesity and gender-specific programming.

Prenatal events appear to program hormonal homeostasis, contributing to the development of somatic disorders at an adult age. The aim of this study was to examine whether maternal exposure to cytokines or to dexamethasone (Dxm) would be followed by hormonal consequences in the offspring at adult age. Pregnant rats were injected on days 8, 10, and 12 of gestation with either human interleukin-6 (IL-6) or tumor necrosis factor-alpha (TNF-alpha) or with Dxm. Control dams were injected with vehicle. All exposed offspring developed increased body weight (P < 0.05--0.001), apparently due to an increase of 30--40% in adipose tissue weight (P < 0.05--0.01). Corticosterone response to stress was increased in the IL-6 group (P < 0.05-0.01). Dxm-treated male rats exhibited blunted Dexamethasone suppression test results. In male rats, insulin sensitivity was decreased after IL-6 exposure (P < 0.01), whereas basal insulin was elevated in the TNF-alpha group (P < 0.01). In female rats, plasma testosterone levels were higher in all exposed groups compared with controls (P < 0.01--0.001), with the exception of Dxm-exposed offspring. Males in the TNF-alpha group showed decreased locomotor activity (P < 0.05), and females in the IL-6 group showed increased locomotor activity (P < 0.05). These results indicate that prenatal exposure to cytokines or Dxm leads to increased fat depots in both genders. In females, cytokine exposure was followed by a state of hyperandrogenicity. The results suggest that prenatal exposure to cytokines or Dxm can induce gender-specific programming of neuroendocrine regulation with consequences in adult life.

Cancer risk in Swedish women: the relation to size at birth.

The relationship between fetal growth as indicated by weight and length at birth, and cancer risk in 1080 adult Swedish women was examined. Birth factors were retrieved from original midwife records for the years 1914, 1918, 1922 and 1930, and primary cancer cases were identified by matching with national and regional cancer registries through the year 1998. A positive and statistically significant increased risk for cancer was found with increasing birth weight or birth length for all site cancer and non-hormone related cancer, defined as all cancer sites excluding breast, uterus and ovary. Addition of factors suspected to influence cancer risk, maternal proteinuria, birth order, own parity and age at menarche, did not attenuate this relation. Previously only breast cancer has been reported to be related to size at birth in adult women and this is the first study to report that cancer sites other than the major hormone-related sites may be influenced by size at birth, as measured by either weight or length at birth; these findings warrant further investigation.

Low IGF-I suppresses VEGF-survival signaling in retinal endothelial cells: direct correlation with clinical retinopathy of prematurity.

Retinopathy of prematurity is a blinding disease, initiated by lack of retinal vascular growth after premature birth. We show that lack of insulin-like growth factor I (IGF-I) in knockout mice prevents normal retinal vascular growth, despite the presence of vascular endothelial growth factor, important to vessel development. In vitro, low levels of IGF-I prevent vascular endothelial growth factor-induced activation of protein kinase B (Akt), a kinase critical for endothelial cell survival. Our results from studies in premature infants suggest that if the IGF-I level is sufficient after birth, normal vessel development occurs and retinopathy of prematurity does not develop. When IGF-I is persistently low, vessels cease to grow, maturing avascular retina becomes hypoxic and vascular endothelial growth factor accumulates in the vitreous. As IGF-I increases to a critical level, retinal neovascularization is triggered. These data indicate that serum IGF-I levels in premature infants can predict which infants will develop retinopathy of prematurity and further suggests that early restoration of IGF-I in premature infants to normal levels could prevent this disease.

Metabolic consequences of different perioperative fluid therapies in the neonatal period.

Carbohydrate and fat metabolism during and after anaesthesia and surgery was studied in 14 neonates with major congenital non-cardiac anomalies. They were either given a glucose solution until surgery or starved for at least 4 h before surgery. Ringer-acetate alone or Ringer-acetate plus 10% glucose was used for the intraoperative fluid therapy. After anaesthesia all neonates were given a 10% glucose solution. Concentrations of glucose, free fatty acids, triglycerides, lactate, pyruvate, alanine, glycerol and 3-hydroxybutyrate were measured at predetermined intervals pre-, intra- and postoperatively. Blood glucose concentrations rose during surgery both in neonates given glucose before and during surgery (n = 6) and in neonates not given glucose before and during surgery (n = 6). Increased intraoperative levels of free fatty acids and 3-hydroxybutyrate were found in neonates not given glucose before and during surgery. The triglyceride levels were equal in both groups. In two neonates given glucose before surgery and Ringer-acetate during surgery increased levels of 3-hydroxybutyrate were found, particularly in one patient who became hypoglycaemic. In conclusion, starved neonates without intraoperative glucose supply mobilized fat and maintained blood glucose concentrations.

Leukotriene B4 and C4 generation by human colostral macrophages in vitro.

To investigate leukotriene (LT) generation by human colostral macrophages (CM phi), we evaluated calcium ionophore A23187-induced LTB4 and LTC4 production by CM phi obtained from mothers who had had preterm and term deliveries. As a comparison, we also investigated such production of these LTs by blood monocytes (BMo). LTB4 and LTC4 production by preterm CM phi did not significantly differ from that by term CM phi. LTB4 and LTC4 production by both preterm and term CM phi was significantly lower than that by BMo. The ratio of LTC4 to LTB4 did not differ significantly between preterm and term CM phi. The CM phi ratios were significantly lower than that of BMo. These findings suggest that human CM phi can generate LTB4 and LTC4 but that production, especially LTC4 production, is suppressed compared with that of BMo.

Influence of fluid regimens on perioperative blood-glucose concentrations in neonates.

Blood concentrations of glucose were measured during surgery and during the first 8 h after operation in 30 neonates undergoing major surgery during the first week of life. Fifteen of the neonates were given Ringer-acetate as the only crystalloid peroperative fluid; to the other 15, 10% glucose i.v. was administered during surgery. In the Ringer-acetate group, mean (SD) blood concentration of glucose increased from 3.1 (2.0) to 4.3 (2.4) mmol litre-1 during surgery. The corresponding increase in the glucose-supplemented group was 3.4 (1.5) to 6.3 (2.2) mmol litre-1. In the Ringer-acetate group, peroperative blood concentrations of glucose were found to be low if a preoperative glucose infusion was interrupted at the start of anaesthesia. Hypoglycaemia occurred in both groups, but more often in the group given Ringer-acetate only (3/15 vs 1/15). Hypoglycaemia was found only in neonates less than 48 h of age and during the first 1 h of anaesthesia only. Monitoring of blood concentrations of glucose and adjustment of the glucose infusion appears to be desirable during and after surgery in neonates.