Vaccination in conservation medicine

Unprecedented human population growth and anthropogenic environmental changes have resulted in increased numbers of people living in closer contact with more animals (wild, domestic, and peridomestic) than at any other time in history. Intimate linkage of human and animal health is not a new phenomenon. However, the global scope of contemporary zoonoses has no historical precedent. Indeed, most human infectious diseases classed as emerging are zoonotic, and many of these have spilled over from natural wildlife reservoirs into humans either directly or via domestic or peridomestic animals. Conservation medicine has recently emerged as a meaningful discipline to address the intersection of animal, human, and ecosystem health. Interest in the development of novel vaccines for wildlife encounters important challenges that may prevent progress beyond the conceptual phase. Although notable examples of successful wildlife immunisation programmes exist, depending upon key considerations, vaccination may or may not prove to be effective in the field. When implemented, wildlife vaccination requires a combination of novel zoonosis pathogen management strategies and public education to balance conservation, economic, and public health issues.     

Absorption/metabolism of sulforaphane and quercetin, and regulation of phase II enzymes, in human jejunum in vivo.

For the first time the human intestinal effective permeability, estimated from the luminal disappearance and intestinal metabolism of phytochemicals, sulforaphane and quercetin-3,4'-glucoside, as well as the simultaneous changes in gene expression in vivo in enterocytes, has been studied in the human jejunum in vivo (Loc-I-Gut). Both compounds as components of an onion and broccoli extract could readily permeate the enterocytes in the perfused jejunal segment. At the physiologically relevant, dietary concentration tested, the average effective jejunal permeability (Peff) and percentage absorbed (+/- S.D.) were 18.7 +/- 12.6 x 10-4 cm/s and 74 +/- 29% for sulforaphane and 8.9 +/- 7.1 x 10-4 cm/s and 60 +/- 31% for quercetin-3,4'-diglucoside, respectively. Furthermore, a proportion of each compound was conjugated and excreted back into the lumen as sulforaphane-glutathione and quercetin-3'-glucuronide. The capacity of the isolated segment to deconjugate quercetin from quercetin-3,4'-diglucoside during the perfusion was much higher than the beta-glucosidase activity of the preperfusion jejunal contents, indicating that the majority (79-100%) of the beta-glucosidase capacity derives from the enterocytes in situ. Simultaneously, we determined short-term changes in gene expression in exfoliated enterocytes, which showed 2.0 +/- 0.4-fold induction of glutathione transferase A1 (GSTA1) mRNA (p < 0.002) and 2.4 +/- 1.2-fold induction of UDP-glucuronosyl transferase 1A1 (UGT1A1) mRNA (p < 0.02). The changes in gene expression were also seen in differentiated Caco-2 cells, where sulforaphane was responsible for induction of GSTA1 and quercetin for induction of UGT1A1. These results show that food components have the potential to modify drug metabolism in the human enterocyte in vivo very rapidly.     

Influence of amikacin as the primary aminoglycoside on bacterial isolates in the intensive care unit

Amikacin was introduced as the primary aminoglycoside in our hospital to prevent the further development of multiply resistant Gram-negative organisms. This study compares clinical and microbiological data before and after institution of this policy to evaluate the influence on clinical outcome in patients as well as changing resistance patterns in the respiratory ICU. Patient populations were similar in terms of severity of illness (Acute Physiology and Chronic Health Evaluation II scores), age, ventilation, invasive procedures, and the incidence of various diseases. We found that the rate of amikacin resistance increased from 8.5% to 39.6% with an increase in resistance to tobramycin (19.3% to 33.3%) and netilmicin (23.9% to 47.9%) over the same period despite minimal usage of these drugs. The clinical outcome was similar in the periods contrasted. Our findings suggest that restricting aminoglycosides to amikacin only resulted in increasing Gram-negative resistance although there was no significant effect on patient outcome.     

Warfarin treatment in patients with atrial fibrillation: Observing outcomes associated with varying levels of INR control

Introduction

We aimed to determine the level of INR control associated with reduced stroke and mortality.

Material and methods

The study used a retrospective cohort design using linked inpatient, haematology and mortality data from Cardiff and the Vale of Glamorgan, UK.Anonymised patients admitted with a diagnosis of non-valvular atrial fibrillation (NVAF) were defined as warfarin or non-warfarin treated by number of repeated International Normalised Ratio (INR) tests. Warfarin treated patients (> 5 INR tests) categorised as at moderate or high risk of stroke (CHADS₂ score ≥ 2) with varying levels of INR control were compared to those who did not receive warfarin treatment using Cox proportional hazards models controlling for age, sex and CHADS₂ score. Outcome measures were time to stroke and mortality.

Results

6,108 patients with NVAF were identified. 2,235 (36.6%) of these patients had five or more INR readings and of these 486 (21.7%) had CHADS₂ score ≥ 2. There was significant improvement in time to stroke event in those patients with INR control of greater than 70% of time in therapeutic range (2.0 to 3.0) compared with the non-warfarin treatment group. Overall survival was significantly improved for all warfarin treated groups with INR control of greater than 40% of time in range.

Conclusions

Patients with INR control of above 70% of time in range had a significantly reduced risk of stroke. Patient suitability for warfarin treatment should be continuously assessed based on their ability to maintain a consistently therapeutic INR.     

The interplay of obesity and asthma

The relationships, interactions, and association between obesity and asthma are complex, and are active sources of hypotheses and research. An association between obesity and asthma has been reported in many studies, although considerable debate about the existence of the association and its meaning still exists. Potential associative relationships may result from genetics, immune system modifications, and mechanical mechanisms. The rising prevalence of asthma and obesity in children and adults, and the significant morbidity from both, make it imperative that clinicians recognize the importance of weight management in patients with and without asthma.     

The challenge of segmental small bowel motility quantitation using MR enterography

Objective:

Analysis of “cine” MRI using segmental regions of interest (ROIs) has become increasingly popular for investigating bowel motility; however, variation in motility in healthy subjects both within and between scans remains poorly described.

Methods:

20 healthy individuals (mean age, 28 years; 14, males) underwent MR enterography to acquire dynamic motility scans in both breath hold (BH) and free breathing (FB) on 2 occasions. Motility data were quantitatively assessed by placing four ROIs per subject in different small bowel segments and applying two measures: (1) contractions per minute (CPM) and (2) Jacobian standard deviation (SD) motility score. Within-scan (between segment) variation was assessed using intraclass correlation (ICC), and repeatability was assessed using Bland–Altman limits of agreement (BA LoA).

Results:

Within-scan segmental variation: BH CPM and Jacobian SD metrics between the four segments demonstrated ICC R = 0.06, p = 0.100 and R = 0.20, p = 0.027 and in FB, the CPM and Jacobian SD metrics demonstrated ICC R = −0.26, p = 0.050 and R = 0.19, p = 0.030. Repeatability: BH CPM for matched segments ranged between 0 and 14 contractions with BA LoA of ±8.36 and Jacobian SD ranged between 0.09 and 0.51 with LoA of ±0.33. In FB data, CPM ranged between 0 and 10 contractions with BA LoA of ±7.25 and Jacobian SD ranged between 0.16 and 0.63 with LoA = ±0.28.

Conclusion:

The MRI-quantified small bowel motility in normal subjects demonstrates wide intersegmental variation and relatively poor repeatability over time.

Advances in knowledge:

This article presents baseline values for healthy individuals of within- and between-scan motility that are essential for understanding how this process changes in disease.Dynamic “cine” MRI acquired during MR enterography is increasingly utilized to assess bowel motility in a range of conditions, notably inflammatory bowel disease and enteric dysmotility syndromes.^1–4 Analysis of the data remains primarily subjective in clinical routine, but the ability to apply quantitative techniques makes this a potentially powerful methodology to explore gastrointestinal physiology in disease as well as an emerging application as a biomarker for drug efficacy.^5–7Despite the growing literature, a consensus has yet to be reached as to the best method of quantitatively analysing small bowel data and indeed a range of motility metrics are proposed.^2,3,8–12 The most commonly used metric is the change in luminal diameter at a fixed anatomical position through the time series. By tracking bowel diameter, a characteristic curve can be produced with the number of contractions expressed per minute (CPM) to give an intuitive and broadly accepted metric for small bowel motility (SBM).^{2–4,9,11,13–15} To date, several studies have reported a relationship between CPM and dysmotility in disease, either compared with a histopathological standard or “normal” reference bowel loops.^2–4,12 An array of additional metrics derived both from bowel diameter measures and more abstract processing techniques have further been implemented with varying degrees of effectiveness in disease and health.^{2,4,5,8,10,14,16}Although intuitively attractive, the robustness of assessing overall enteric motility using only an isolated loop of bowel has received relatively little attention to date irrespective of the precise metric applied. It is unclear how representative the selected bowel loops are of overall SBM and if normal motility intrinsically differs between bowel segments, for example, between the jejunum and ileum. Furthermore, the repeatability of single loop metrics, even in normal individuals, is not well described, knowledge of which is vital if segmental analysis is to be used to diagnose, guide treatment and monitor enteric pathology.The purpose of this study is to explore segmental variation in SBM in healthy volunteers measured using two commonly reported small bowel metrics [CPM and Jacobian standard deviation (SD)] looking at (1) within-scan motility variation between different segments and (2) between-scan variation (repeatability) across two time points.     

Left ventricular lead implantation in an unusual anatomy of the proximal coronary sinus

A 62-year-old man with Class III heart failure and left bundle branch block underwent cardiac resynchronization therapy. Because prior implantation attempts from the left side were unsuccessful, the right side approach was attempted. However, it was still impossible to advance the pre-shaped sheaths into the distal coronary sinus (CS) because the CS was abnormal with a posterior vertical take off followed by a sharp sigmoid curve before the AV groove. Ultimately, a straight sheath was adjusted to fit the sigmoid curve with the guidance of an electrophysiologic catheter and a left ventricular lead was then passed into the anterolateral vein. There was no financial support for this study.     

Elevated mutation rates in the germ line of first- and second-generation offspring of irradiated male mice

Mutation rates at two expanded simple tandem repeat loci were studied in the germ line of first- and second-generation offspring of inbred male CBA/H, C57BL/6, and BALB/c mice exposed to either high linear energy transfer fission neutrons or low linear energy transfer x-rays. Paternal CBA/H exposure to either x-rays or fission neutrons resulted in increased mutation rates in the germ line of two subsequent generations. Comparable transgenerational effects were observed also in neutron-irradiated C57BL/6 and x-irradiated BALB/c mice. The levels of spontaneous mutation rates and radiation-induced transgenerational instability varied between strains (BALB/c>CBA/H>C57BL/6). Pre- and postmeiotic paternal exposure resulted in similar increases in mutation rate in the germ line of both generations of CBA/H mice, which together with our previous results suggests that radiation-induced expanded simple tandem repeat instability is manifested in diploid cells after fertilization. The remarkable finding that radiation-induced germ-line instability persists for at least two generations raises important issues of risk evaluation in humans.