Reported analgesic administration to rabbits undergoing experimental surgical procedures

Background  

It has become widely accepted that whenever animals are used in scientific procedures, the 3Rs principle of replacement, reduction and refinement described by William Russell and Rex Burch should be adhered to. Animals should be replaced with non-sentient alternatives if possible, the number of animals used should be reduced and experimental procedures should be refined to minimise pain, suffering and distress. Administration of analgesic agents to animals undergoing surgical procedures is a refinement used to alleviate pain. In this study, a structured literature review was carried out to examine current trends in analgesic administration to rabbits undergoing experimental surgical procedures.     

Experimental mycosis in immunosuppressed rabbits

Chronic candidosis was established in rabbits by the injection I.V. of 2×10⁶ cells of C. albicans. The rabbits were assayed every week for 14 weeks for the appearance of Candida antigen and anticandida antibodies in serum and other body fluids. Tests were carried out in double diffusion plates; antigen against hyperimmune rabbit sera and antibody against Candida cell sap antigen preparation. A sensitive specific passive hemagglutination procedure was also developed which used chromate treated cells. In rabbits with chronic candidosis not treated with cyclophosphamide antigen was detected in 4x concentrated serum between the fifth and sixth week. At about the same time antibodies were demonstrable and theafter antigen was no longer detected. Maximum antibody titer occurred between the eight to 10th week and disappeared thereafter. If cyclophosphamide 30 mg/kg was given at this point, anticandida antibodies reappeared in high titers, persisted for three to four weeks and then disappeared. At autopsy no evidence of candidosis was present. If rabbits were pretreated with cyclophosphamide 60 mg/kg for one week before inoculation and given the drug weekly thereafter no antibody was detectable but antigen and antibody were present in body fluids (not serum) at post mortem.Supported by grant number 1-PO1-CA-19266-01 from the National Cancer Institute, United States Public Health Service.Presented at the 4th International Conference of the Mycoses, Brazilia, Brazil, 1977.     

Experimental congenital syphilis in rabbits

A model for congenital syphilis in rabbits was developed based on multiple intravenous injections of pregnant does with high concentrations of Treponema pallidum. A total of 48 pregnant does and 394 newborns were evaluated. Indications of in utero infection included a 7- to 10-fold increase in fetal mortality and a 49% reduction in birth weight. The size of the stillborns varied. Some developed to normal size, whereas others were poorly developed, hemorrhagic, and 1/10th normal size. Fetuses were surgically removed after 25 to 28 days of gestation and extracts of the fetal tissues were injected into adult rabbits. Syphilitic lesions resulted demonstrating the presence of T. pallidum within the fetal tissues. Treponemes were also demonstrated within splenic tissue from a 1-week-old newborn. Isolated amniotic membranes were placed in Franz Biologic chambers. Viable organisms readily penetrated through the amnion but heat-inactivated organisms did not. Further evidence for in utero transmission of organisms was provided by intradermal injection of 6- to 7-week-old newborns. In control newborns in which the does were not infected during pregnancy, lesions occurred at 90% of the sites injected and developed in typical fashion. In newborns from does infected during pregnancy, lesions occurred in 18% of the sites injected and developed in atypical fashion (flat, nonulcerating, rapid healing). Finally, overt congenital syphilis did not occur if the does were immune prior to pregnancy, then infected with T. pallidum during pregnancy. The percent mortalities and birth weights of newborns were equivalent to control newborns from noninfected does.     

Gene transfer during surgical procedures with molecular surgical suture

Over the last decades, there has been an explosion of interest in plasmid DNA for gene therapy with reports of their efficacy in the fight against cancer, vascular diseases, and inherited diseases caused by specific gene defects (Srivastava, 2003). DNA plasmids present several advantages over the use of recombinant viruses concerning their production and safety issues. Plasmid DNA vectors can be constructed easily and economically, and they are free of size constraints imposed by viral packaging, obviating the need for an infectious vector and lessening the likelihood of toxicity and immunogenicity (Davis, 1993). Plasmids have a relative low cost, long shelf life and allow repetitive administration of the therapeutic gene without generating an immune response against the delivery vector (Donnelly, 2003). Finally, plasmids can be injected directly into tissues, such as heart (Sarkar, 2002), muscle (Neumeister, 2001, Dan, 2000) and tumors (De Marco, 2003, Sasaki, 2002).     

Preoperative testing before low-risk surgical procedures

Background:There is concern about increasing utilization of low-value health care services, including preoperative testing for low-risk surgical procedures. We investigated temporal trends, explanatory factors, and institutional and regional variation in the utilization of testing before low-risk procedures.Methods:For this retrospective cohort study, we accessed linked population-based administrative databases from Ontario, Canada. A cohort of 1 546 223 patients 18 years or older underwent a total of 2 224 070 low-risk procedures, including endoscopy and ophthalmologic surgery, from Apr. 1, 2008, to Mar. 31, 2013, at 137 institutions in 14 health regions. We used hierarchical logistic regression models to assess patient- and institution-level factors associated with electrocardiography (ECG), transthoracic echocardiography, cardiac stress test or chest radiography within 60 days before the procedure.Results:Endoscopy, ophthalmologic surgery and other low-risk procedures accounted for 40.1%, 34.2% and 25.7% of procedures, respectively. ECG and chest radiography were conducted before 31.0% (95% confidence interval [CI] 30.9%–31.1%) and 10.8% (95% CI 10.8%–10.8%) of procedures, respectively, whereas the rates of preoperative echocardiography and stress testing were 2.9% (95% CI 2.9%–2.9%) and 2.1% (95% CI 2.1%–2.1%), respectively. Significant variation was present across institutions, with the frequency of preoperative ECG ranging from 3.4% to 88.8%. Receipt of preoperative ECG and radiography were associated with older age (among patients 66–75 years of age, for ECG, adjusted odds ratio [OR] 18.3, 95% CI 17.6–19.0; for radiography, adjusted OR 2.9, 95% CI 2.8–3.0), preoperative anesthesia consultation (for ECG, adjusted OR 8.7, 95% CI 8.5–8.8; for radiography, adjusted OR 2.2, 95% CI 2.1–2.2) and preoperative medical consultation (for ECG, adjusted OR 6.8, 95% CI 6.7–6.9; for radiography, adjusted OR 3.6, 95% CI 3.5–3.6). The median ORs for receipt of preoperative ECG and radiography were 2.3 and 1.6, respectively.Interpretation:Despite guideline recommendations to limit testing before low-risk surgical procedures, preoperative ECG and chest radiography were performed frequently. Significant variation across institutions remained after adjustment for patient- and institution-level factors.In response to concerns about increasing utilization of low-value health care services, the American Board of Internal Medicine Foundation launched the Choosing Wisely campaign in the United States in 2012.¹ The goal of the campaign is to encourage conversations between physicians and patients about low-value care by defining “top 5” lists of tests, treatments and procedures that may be unnecessary or unsupported by evidence.¹ Subsequent Choosing Wisely campaigns have followed in other countries, including Canada starting in April 2014.^2,3 Of interest for health policy-makers, payers and clinicians are current utilization rates for the procedures mentioned in these recommendations. Establishing baseline rates permits an understanding of the extent of the problem of low-value care, which in turn allows monitoring of the effect of initiatives such as Choosing Wisely on utilization rates over time.One Choosing Wisely item included by many specialty societies is the recommendation to avoid routinely performing preoperative testing (including chest radiography, echocardiography and cardiac stress tests) for patients undergoing low-risk surgery.^4–6 This recommendation was previously included in the 2007 American College of Cardiology/American Heart Association guidelines on perioperative cardiovascular evaluation for noncardiac surgery⁷ and was reconfirmed in a recent update.⁸ Avoiding preoperative investigations in this setting is supported by evidence that routine testing in patients undergoing low-risk surgery does not improve outcomes or change management and may lead to further unnecessary downstream testing, cancellation of surgery, and increases in patient anxiety and cost.^7,9–12 To date, neither the rate of preoperative testing across a large and diverse jurisdiction nor the degree of variation at regional and institutional levels, where data may be “actionable,” is well understood.The objectives of this study were to determine utilization rates of preoperative tests before hospital-based low-risk surgical procedures at the jurisdictional, regional and institutional level. In addition, we aimed to evaluate temporal trends of preoperative testing over a 5-year period. We hypothesized that there would be significant regional and institutional variation in preoperative cardiac testing before low-risk surgery and that patients with prior cardiac comorbidities would have a higher rate of preoperative testing than those without such comorbidities.     

Experimental pulmonary candidiasis in modified rabbits

Pulmonary lesions induced by an intratracheal inoculation of Candida albicans into rabbits in untreated control, bovine serum albumin (BSA)-sensitized and C. albicans-sensitized groups were examined immunohistochemically to clarify the localization of IgG, IgM and C3. In the control group no inflammatory cells were immunoreactive for IgG and only a few macrophages for IgM and C3, whereas in the BSA- and C. albicans-sensitized groups there were a small number of IgG-positive polymorphonuclear leukocytes and IgM- and C3-positive macrophages in the lesions, the latter group being more prominent. Furthermore, epithelioid granulomatous lesions at the late stage in the C. albicans-sensitized animals showed scattered epithelioid cells containing IgG as well as abundant IgG- and IgM-positive plasma cells. These immunohistochemical results were considered to support the estimation that immune complexes contributed to the modification of fungal lesions in the C. albicans-sensitized hosts, although non-immunological defense mechanisms seemed to be more important in the elimination of the fungus.     

Experimental unilateral coronal synostosis in rabbits

Immobilization of the coronal suture was produced unilaterally in 9-day-old rabbits to determine its effect on subsequent craniofacial development. The suture was immobilized unilaterally by the topical application of methylcyanoacrylate adhesive. Subsequent growth effects on the cranial vault, base, and facial skeleton were assessed by serial radiographic cephalometry. Unilateral coronal suture immobilization resulted in significantly decreased bone growth at the coronal suture (mean 0.95 mm +/- 0.35 SE) when compared to sham-treated control animals (mean 5.06 mm +/- 0.20 SE). Frontonasal suture bone growth contralateral to the immobilized half of the coronal suture, however, was significantly increased. The anterior cranial base became significantly shortened, and orbital asymmetry developed. The pattern of induced abnormalities simulates unilateral coronal synostosis in humans.     

Experimental pulmonary candidiasis in modified rabbits

The present experiment was performed in order to analyze and compare the histopathological features of Candida infection in various states of host defense capacity. The pulmonary lesions were induced by an intratracheal inoculation of 10⁸ live cells of Candida albicans into each of the rabbits in the following 4 groups: 1) untreated controls, 2) animals sensitized non-specifically to bovine serum albumin (BSA), 3) those sensitized specifically to formalin-killed C. albicans cells, and 4) those treated with cyclophosphamide and mitomycin C. The animals were sacrificed at appropriate intervals up to 16 days after inoculation. At autopsy, the lungs were cultured and then subjected to histopathological, electron microscopic and enzyme cytochemical examinations.In the healthy control animals, the fungal lesions consisted of polymorphonuclear leukocytes (PMN) at the initial stage, gradually changing to granulomatous inflammation, which contained no peroxidase-positive macrophages. In the animals sensitized non-specifically to BS A exudative macrophages appeared in the lesions, the nature of which did not differ from that of the control animals. In the animals sensitized specifically to Candida cells, more extensive infiltration of PMN was observed at the initial stage, a fact which may suggest the participation of the Arthus phenomenon in the development of the lesions. Furthermore, an epithelioid cell transformation of the macrophages in the granulomatous lesions may also suggest that immune complexes contributed to their formation. In the drug-treated animals, the lesions consisted of necrotic or less prominent cellular foci which correspond to the features of human candidiasis in debilitated states, and the inoculated fungi grew progressively to form pseudohyphae. An asteroid structure protruding radially from the surface of the fungal cells and attaching to primary lysosomes in the phagocytes was observed occasionally. This structure seems to be formed when the function of the phagocytes in the defense mechanisms against the fungi is suppressed to some extent.From the results of the present experiment, we would emphasize that PMN play an initial role in the elimination of C. albicans cells in the lung, and that macrophages then contribute to the formation of the lesions immunologically or non-immunologically.     

不同手术方式对VX2肿瘤侵犯兔下腔静脉预后的影响

目的建立VX2肿瘤侵犯下腔静脉（inferior vena cava,IVC）的动物模型,观察3种不同手术方式对实验动物预后的影响。方法成功建立VX2肿瘤侵犯IVC的动物模型,彩超下证实;将实验动物随机均分为A、B、C三组,分别予以彻底切除IVC和肿瘤、不予重建、彻底切除后人工血管进行重建处理,切下的IVC均送病检。分别于手术后每周彩超观察IVC,出现闭塞的IVC在DSA（digtal subtraction angiography,DSA）下观察侧枝循环建立情况。观察实验动物自然死亡时间,并解剖。结果超声发现3周时所有实验动物均有肿瘤生长（2.75±0.91cm2）,IVC管腔无明显狭窄（2.53±0.23 mm）;DSA显示,人工血管中长期通畅率低,随时间变化实验组可见侧支循环建立和腹壁浅静脉增粗逆流;A、B两实验组生存时间显著高于对照组C组（P1〈0.05;P2=0.036〈0.05）;两实验组中A组生存时间显著高于B组（P3=0.04〈0.05）。两实验组远处转移无差异,均显著低于对照组。结论彻底切除肿瘤可以提高实验动物的术后生存时间和生存率;兔IVC人工血管重建中长期通畅率低,且围手术期死亡率高,生存时间也较不重建组低。     

Mechanical considerations in the design of surgical reconstructive procedures

Tendon transfers are used to restore arm and hand function after injury to the peripheral nerves or after spinal cord injury. Traditional guidelines to choose the length at which the transferred muscle should be attached have a poor scientific foundation. We postulate that passive tension only becomes significant at relatively long lengths and that passive tension as the major factor in intra-operative decision making may result in overstretch of the muscle-tendon unit (MTU) and accompanying low-active force generation. It appears unwise to rely on unknown factors, such as slippage or stress relaxation, to correct an overstretched transfer. Instead, we suggest the use of intra-operative sarcomere length measurements to predict and set the optimal MTU length during reconstructive upper limb surgery.