Characteristics of Vibration that Alter Cardiovascular Parameters in Mice

We hypothesized that short-term exposure of mice to vibration within a frequency range thought to be near the resonant frequency range of mouse tissue and at an acceleration of 0 to 1 m/s² would alter heart rate (HR) and mean arterial pressure (MAP). We used radiotelemetry to evaluate the cardiovascular response to vibration in C57BL/6 and CD1 male mice exposed to vertical vibration of various frequencies and accelerations. MAP was consistently increased above baseline values at an acceleration near 1 m/s² and a frequency of 90 Hz in both strains, and HR was increased also in C57BL/6 mice. In addition, MAP increased at 80 Hz in individual mice of both strains. When both strains were analyzed together, mean MAP and HR were increased at 90 Hz at 1 m/s², and HR was increased at 80 Hz at 1 m/s². No consistent change in MAP or HR occurred when mice were exposed to frequencies below 80 Hz or above 90 Hz. The increase in MAP and HR occurred only when the mice had conscious awareness of the vibration, given that these changes did not occur when anesthetized mice were exposed to vibration. Tested vibration acceleration levels lower than 0.75 m/s² did not increase MAP or HR at 80 or 90 Hz, suggesting that a relatively high level of vibration is necessary to increase these parameters. These data are important to establish the harmful frequencies and accelerations of environmental vibration that should be minimized or avoided in mouse facilities.Abbreviations: HR, heart rate; MAP, mean arterial pressure; RFR, resonance frequency rangeExcessive levels of vibration are widely seen as a potential cause of organ injury and physiologic changes in laboratory animals, including altered heart rate (HR), mean arterial pressure (MAP), and circadian rhythm;^15,19,20 therefore, vibration can affect animal welfare or research integrity. Sources of vibration in animal facilities are diverse and difficult to control. Vibration can be generated by components of the animal care facility, including cage wash equipment, autoclaves, animal transfer stations, and ventilated racks as well as by physical plant construction²² and municipal traffic near the animal facility. Moreover, the frequencies and acceleration of vibration that induce physiologic changes are not well known. Studies performed in humans^4-7 have shown that exposure to prolonged vibration at an acceleration of 0.5 m/s² for 8 h induces harmful effects.²³ Vertical vibration at frequencies of 0 to 63 Hz is reported to be most harmful in humans.²⁵ Although vibration can be detrimental to laboratory animals, a concern expressed in the new edition of the Guide for the Care and Use of Laboratory Animals,¹⁴ no information is currently available concerning the frequency ranges or acceleration that exert harmful effects in laboratory animals.The resonance frequency range (RFR) is the range of frequencies at which an object most readily vibrates and the range over which an animal may sense, respond to, and suffer adverse effects from vibration.^12,13 Our laboratory has established that the approximate RFR for mice is 31 to 100 Hz at 0.3 to 1.0 m/s², with most individual mice registering RFR values lower than 80 Hz.²⁷ However the physiologic effects of vibration in this range have not been determined. The goal of the current study was to determine whether vibration-induced changes in MAP and HR occurred within this frequency range.When testing the adverse effects of vibration or sound it is necessary to determine which of these play a larger role in inducing physiologic changes; this task is challenging because both sound and vibration can occur concomitantly. Delineating the separate contributions of sound and vibration in causing adverse effects and the mechanism whereby these occur need to be addressed when studying the adverse effects of vibration in animals. The current study determines the effects of vibration on MAP and HR in the absence of a contribution of sound to changes in these parameters.Stress is a leading risk in the development of cardiovascular disease.¹¹ In laboratory animals, stress can cause cardiovascular, neuroendocrine, and immunologic changes,^3,9,26,31 and previous research has demonstrated that vibration can cause disorders of the central autonomic nervous system.²¹ This component of the nervous system helps to control MAP, HR, peripheral blood flow, digestion, and respiratory rate as well as other physiologic processes. Animal distress would be presumed to be the reason for any changes in cardiovascular parameters due to vibration, but previous research showed that vibration caused increases in blood flow and pressure in anesthetized dogs and pigs.¹⁰ We used radiotelemetry to study vibration-induced changes in MAP and HR in conscious and anesthetized mice to determine whether anesthesia mitigated these changes.Currently there are no direct data regarding the frequencies and accelerations of vibration that produce physiologic changes in mice. Our goal was to test the hypotheses that mechanical vibration of 31 to 100 Hz induces changes in MAP and HR in conscious mice. In addition, these experiments established the minimal levels of acceleration required to cause these changes. Therefore, our findings help to establish standards against which environmental vibration can be compared and assessed to estimate potential effects on animal wellbeing and research outcomes.     

Faecal calprotectin levels in a high risk population for colorectal neoplasia

BACKGROUND: Faecal concentrations of the protein calprotectin have been found to be elevated in patients with colorectal neoplasia, suggesting that it might be used as a screening tool for colorectal cancer as well as adenomas. AIMS: To measure the sensitivity and specificity of faecal calprotectin for the detection of adenomas in high risk individuals undergoing colonoscopy. Also, to investigate between and within stool variability of calprotectin concentrations. SUBJECTS: A total of 814 patients planned for colonoscopy were included for the following indications: positive faecal occult blood test, 25; neoplasia surveillance, 605; newly detected polyp, 130; and family risk, 54. METHODS: Two faecal samples from each of two stools were analysed using the PhiCal ELISA test device (Nycomed Pharma AS). RESULTS: Adenoma patients had significantly higher calprotectin levels than normal subjects (median 9.1 (95% confidence interval 7.5-10.1) v 6.6 (5.6-7.4)mg/l). There was no significant decrease in calprotectin levels after polypectomy. Levels in cancer patients were significantly higher than those in all other subgroups (median 17.6 mg/l (11.5-31.0)). With a cut off limit of 10 mg/l, the sensitivity for cancer was 74% and for adenoma 43%. Corresponding specificity values were 64% for no cancer and 67% for no neoplasia (cancer+adenoma). Specificity varied from 71% for one stool sample to 63% for four samples. Stool variability was small, suggesting that two spots from one stool were as discriminative as two spots from each of two stools. CONCLUSIONS: The sensitivity and specificity of faecal calprotectin levels as a marker for colorectal adenoma and carcinoma justifies its use in high risk groups, but specificity is too low for screening of average risk persons. Lack of a decrease in levels after polypectomy may be due to a more widespread leucocyte migration into the intestinal lumen than that at the polyp site, and needs further investigation.     

The occurrence of different levels of G gamma chain and of the A gamma T variant of fetal hemoglobin in newborn babies from several countries

The gamma chain compositions of the fetal hemoglobins of 2453 newborn babies from East Asian countries (1350 babies), from Italy, Yugoslavia, Bulgaria, and Georgia (417 Caucasian babies), and 686 black babies from Georgia were determined by high pressure liquid chromatography. Unusual results for a limited number of babies were confirmed by chemical analyses, and were evaluated further by family studies. Statistical analyses indicated high gene frequencies for the A gamma T chain in Italian (f = 0.237), Yugoslavian and Bulgarian (f = 0.238), and white Georgia babies (f = 0.224), a lower frequency in Japan (f = 0.178), and India (f = 0.173), and particularly in mainland China (f = 0.079). The A gamma T gene frequency in normal (AA) Black babies was 0.102. When a beta S or beta C mutation was also present this frequency was greatly decreased, particularly in babies with the AC condition (f = 0.036). These results suggest the near absence of the A gamma T mutation on the chromosome also carrying the beta C determinant. Most babies had the expected G gamma values which vary between 60 and 80%, but several (mainly black) babies had higher values (between 80 and 90%), while one normal black baby had a G gamma value of (nearly) 100%. This condition may be a form of A gamma +1-thalassemia and has been discussed in detail elsewhere (Blood 58:491-500, 1981). Thirty-five clinically normal (mainly Chinese, Indian, and Japanese) babies had G gamma values of about 40%. Twenty-six babies had A gamma I values of about 60%, while the remaining nine babies had A gamma T and A gamma I chains in a ratio of either 1 to 2 or 1 to 1. Two additional newborns did not produce any G gamma chains, but had only A gamma I chains or A gamma T chains. Family studies failed to indicate a specific hematological abnormality. These unusual ratios between the G gamma and A gamma (either A gamma I or A gamma T) chains have led to speculations regarding possible genetic abnormalities present in these infants.     

Biocompatibility and Osteogenic/Calcification Potential of Casein Phosphopeptide-amorphous Calcium Phosphate Fluoride

Introduction

Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and CPP-ACP with fluoride (CPP-ACFP) have been shown to provide bioavailable ions to promote mineralization. Hence, the aim of this study was to evaluate the materials’ biocompatibility and osteogenic/calcification potential for endodontic applications.

Retention of knowledge of the Paediatric Life Support guidelines

Paediatric Life Support (PLS) courses are thought to significantly increase knowledge of paediatric resuscitation for all professional groups. PLS and Newborn Life Support (NLS) guidelines were revised and updated in 2005. In a telephonic survey, the retention and awareness of the changes in PLS guidelines were evaluated among 100 junior paediatric doctors. Overall, second on-call doctors tended to score higher than the first on-call doctors (score 6.55 ± 2.25 vs. 5.89 ± 2.17 respectively, p = 0.062). Doctors who attended PLS courses after 2005 tended to have higher scores. There is a need to streamline formalised regular updates (e.g. annual online written multiple choice questions) and in-house rehearsals using mock emergency scenarios at local, regional and national level.     

Long-Term Follow-up of Lobular Neoplasia (Atypical Lobular Hyperplasia/Lobular Carcinoma In Situ) Diagnosed on Core Needle Biopsy

Background

Lobular neoplasia (LN) includes atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS). LN often is an incidental finding on breast core needle biopsy (CNBx) and management remains controversial. Our objective was to define the incidence of malignancy in women diagnosed with pure LN on CNBx, and identify a subset of patients that may be observed.

Methods

Patients diagnosed with LN on CNB between January 1993 and December 2010 were identified. Patients with an associated high-risk lesion or ipsilateral malignancy at time of diagnosis were excluded. All cases were reviewed by dedicated breast pathologists and breast imagers for pathologic classification and radiologic concordance, respectively.

Results

The study cohort was comprised of 184 (1.3?%) cases of pure LN (147 ALH, 37 LCIS) from 180 patients. Pathologic?Cradiologic concordance was achieved in 171 (93?%) cases. Excision was performed in 101 (55?%) cases and 83 (45?%) were observed. Mean follow-up was 50.3 (range, 6?C212) months. Of cases excised, 1 of 81 (1.2?%) ALH and 1 of 20 (5?%) LCIS cases were upstaged to ductal carcinoma in situ (DCIS) and invasive lobular carcinoma (ILC), respectively. Only 1 of 101 (1?%) concordant lesions was upstaged on excision. Of the cases observed, 4 of 65 (6.2?%) developed ipsilateral cancer during follow-up: 1 of 51 (2?%) case of ALH and 3 of 14 (21.4?%) cases with LCIS (2 ILC, 2 DCIS). During follow-up, 2.9?% (4/138) patients with excised or observed LN developed a contralateral cancer.

Conclusions

These data support that not all patients with LN diagnosed on CNB require surgical excision. Patients with pure ALH, demonstrating radiologic?Cpathologic concordance, may be safely observed.     

System‐based factors influencing intraoperative decision‐making in rectal cancer by surgeons: an international assessment

Aim Sound surgical judgement is the goal of training and experience; however, system‐based factors may also colour selection of options by a surgeon. We analysed potential organizational characteristics that might influence rectal cancer decision‐making by an experienced surgeon. Method One hundred and seventy‐three international centres treating rectal cancer were invited to participate in a survey assessment of key treatment options for patients undergoing curative rectal‐cancer surgery. The key organizational characteristics were analysed using multivariate methods for association with intra‐operative surgical decision‐making. Results The response rate was 71% (123 centres). Sphincter‐saving surgery was more likely to be performed at university hospitals (OR = 3.63, P = 0.01) and by high‐caseload surgeons (OR = 2.77 P = 0.05). A diverting stoma was performed more frequently in departments with clinical audits (OR = 3.06, P = 0.02), and a diverting stoma with coloanal anastomosis was more likely in European centres (OR = 4.14, P = 0.004). One‐stage surgery was less likely where there was assessment by a multidisciplinary team (OR = 0.24, P = 0.02). Multivariate analysis showed that university hospital, clinical audit, European centre, multidisciplinary team and high caseload significantly impacted on surgical decision‐making. Conclusion Treatment variance of rectal cancer surgeons appears to be significantly influenced by organizational characteristics and complex team‐based decision‐making. System‐based factors may need to be considered as a source of outcome variation that may impact on quality metrics.