Drunken lamb syndrome (DLS) is a fatal disease of unknown aetiology affecting young lambs. In 2011, a prospective on farm cohort study was carried out to investigate the epidemiology and pathophysiology of DLS. Ten cases from a cohort of 1635 crossbred and pure Welsh Mountain lambs were identified as having DLS on the basis of characteristic clinical signs. Renal histopathology demonstrated nephrosis in all 10 cases. Some cases also demonstrated concurrent intestinal pathology. The cases were significantly smaller than the cohort, nine out of the 10 were twins, and they all demonstrated a severe metabolic acidosis characterised by elevated D-lactate. This study demonstrates that D-lactate--probably initiated by the overgrowth of intestinal microorganisms--appears to be the cause of the metabolic acidosis seen in cases of DLS, and to be responsible for the clinical signs seen. It is unclear as to the significance of the nephrosis lesions, and the name 'Lamb Nephrosis' may be misleading. Treatment may be possible using solutions of sodium bicarbonate.

Drunken lamb syndrome (DLS) has recently been described as lamb D-lactic acidosis syndrome (LDLAS). In 2012, 18 lambs aged between 7 days and 28 days with LDLAS were identified. Biochemically, each lamb had a metabolic acidosis characterised by D-lactic acidosis and exhibited clinical signs including: not hyperthermic, no evidence of dehydration, demonstrating an ataxic gait tending to recumbency (DLS) and possibly somnolence. These lambs received 50 mmol of sodium bicarbonate as an 8.4 per cent solution given orally, together with parenteral long-acting amoxicillin. All 18 cases made a full clinical recovery. This study demonstrates a novel effective treatment for a disease that is usually fatal, and also demonstrates a strong correlation between venous plasma bicarbonate concentrations and venous plasma D-lactate concentrations (R(2)=0.49).

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Background: Vitamin D may be important in the causal pathway to breast cancer (BC) by influencing breast density, a potential intermediate biomarker for carcinogenesis. However, previous study results are inconsistent, particularly among postmenopausal women. Our objectives were to prospectively examine the relationship between blood biomarkers of vitamin D (serum 25-OH-D) and mammographic breast density (MD) in postmenopausal women at northern latitudes. Potential effect modifications by calcium or exemestane therapy on the relationship between serum 25-OH-D and follow-up MD were also examined. Methods: The NCIC Clinical Trials Group conducted a randomized controlled trial (RCT) comparing exemestane (E) with placebo (P) in 4560 postmenopausal women at high risk for developing BC (MAP.3) (Goss, NEJM 2011). Using a nested observational design, we evaluated a cohort of participants from across Canada and Buffalo, NY. BC risk factor information was previously collected; primary exposure and outcome data were obtained from serum samples and mammograms. Serum 25-OH-D was measured using state-of-the-art LC-MS/MS from samples collected at baseline and year 1. Values for year 1 samples were adjusted to match the month of sampling for the baseline sample month and these samples were averaged. Baseline and ≥ 3 year follow-up percent MD were centrally assessed, blinded to treatment allocation and vitamin D levels, using Cumulus software. Linear regression was used to estimate the effect of serum 25-OH-D on log transformed percent MD at ≥ 3 year follow-up controlling for month of sampling and potential confounders of age, body mass index, first degree family history of BC and calcium. Results: Percent MD was measured for 568 participants (E=287, P=281) with a ≥ 3 year follow-up mammogram obtained from 21 (91%) Canadian sites participating in MAP.3 and one US site in Buffalo, NY. The mean age of these women at study entry was 62 years and they were followed for a mean of 3.7 years. The geometric mean percent MD of the follow-up mammograms was 4.3%. A random sample of 10% (N=102) of mammograms was repeated with high intra-rater reliability (correlation coefficient = 0.95). Unadjusted for month of blood collection, the mean serum 25-OH-D concentration was 36.5 ng/mL (SD=10.6) based on pooled baseline and year one serum samples. After controlling for month of sampling and potential confounders, serum 25-OH-D was not predictive of log transformed percent MD (p=0.25). Statistically significant interactions with calcium (above vs. below the median calcium value p=0.30) or exemestane (p=0.99) on the serum 25-OH-D and MD relationship were not detected. Preliminary results suggest some evidence that low vitamin D (<25 ng/mL) is associated with increased breast density in the presence of low calcium. Final results will be reported at the time of the AACR meeting. Conclusion: In this nested observational study, no association between serum 25-OH-D levels and percent MD at ≥ 3 year follow-up was detected after controlling for month of sampling and many well established BC risk factors. This study was funded by the Canadian Breast Cancer Foundation. The MAP.3 trial was supported by Pfizer. The NCIC CTG is supported by the Canadian Cancer Society Research Institute. Citation Format: Melanie Walker, Harriet Richardson, Paul Goss, Doris Jabs, Glenville Jones, Martin Kaufmann, Jean Wactawski-Wende, Angela Cheung, Eric Winquist, Silvana Spadafora, Susan Ellard, Amanda Hey, Andrew Cooke, Andrea Eisen, Shailendra Verma, Lavina Lickley, Dongsheng Tu, Karen Gelmon, Ralph Meyer, Will King. Vitamin D and mammographic density in postmenopausal women: A cohort study nested within the NCIC CTG MAP.3 chemoprevention trial. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B97.