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Genomic rearrangements (gross chromosomal rearrangements, GCRs) threatens genome integrity and cause cell death or tumor formation. At the terminus of linear chromosomes, a telomere-binding protein complex, called shelterin, ensures chromosome stability by preventing chromosome end-to-end fusions and regulating telomere length homeostasis. As such, shelterin-mediated telomere functions play a pivotal role in suppressing GCR formation. However, it remains unclear whether the shelterin proteins play any direct role in inhibiting GCR at non-telomeric regions. Here, we have established a GCR assay for the first time in fission yeast and measured GCR rates in various mutants. We found that fission yeast cells lacking shelterin components Taz1 or Rap1 (mammalian TRF1/2 or RAP1 homologues, respectively) showed higher GCR rates compared to wild-type, accumulating large chromosome deletions. Genetic dissection of Rap1 revealed that Rap1 contributes to inhibiting GCRs via two independent pathways. The N-terminal BRCT-domain promotes faithful DSB repair, as determined by I-SceI-mediated DSB-induction experiments; moreover, association with Poz1 mediated by the central Poz1-binding domain regulates telomerase accessibility to DSBs, leading to suppression of de novo telomere additions. Our data highlight unappreciated functions of the shelterin components Taz1 and Rap1 in maintaining genome stability, specifically by preventing non-telomeric GCRs.

DNA double-strand breaks (DSBs) activate the DNA damage checkpoint machinery to pause or halt the cell cycle. Telomeres, the specific DNA-protein complexes at linear eukaryotic chromosome ends, are capped DSBs that do not activate DNA damage checkpoints. This “checkpoint privileged” status of telomeres was previously investigated in the yeast Schizosaccharomyces pombelacking the major double-stranded telomere DNA binding protein Taz1. Telomeric DNA repeats in cells lacking Taz1 are 10 times longer than normal and contain single-stranded DNA regions. DNA damage checkpoint proteins associate with these damaged telomeres, but the DNA damage checkpoint is not activated. This severing of the DNA damage checkpoint signaling pathway was reported to stem from exclusion of histone H4 lysine 20 dimethylation (H4K20me2) from telomeric nucleosomes in both wild type cells and cells lacking Taz1. However, experiments to identify the mechanism of this exclusion failed, prompting our re-evaluation of H4K20me2 levels at telomeric chromatin. In this short report, we used an extensive series of controls to identify an antibody specific for the H4K20me2 modification and show that the level of this modification is the same at telomeres and internal loci in both wild type cells and those lacking Taz1. Consequently, telomeres must block activation of the DNA Damage Response by another mechanism that remains to be determined.

DNA double-strand (DSBs) breaks activate the DNA damage checkpoint machinery to pause or halt the cell cycle. Telomeres, the specific DNA-protein complexes at linear eukaryotic chromosome ends, are capped DSBs that do not activate DNA damage checkpoints. This “checkpoint privileged” status of telomeres was previously investigated in the yeast Schizosaccharomyces pombe lacking the major double-stranded telomere DNA binding protein Taz1. Telomeric DNA repeats in cells lacking Taz1 are 10 times longer than normal and contain single-stranded DNA regions. DNA damage checkpoint proteins associate with these damaged telomeres, but the DNA damage checkpoint is not activated. This severing of the DNA damage checkpoint signaling pathway was reported to stem from exclusion of histone H4 lysine 20 dimethylation (H4K20me2) from telomeric nucleosomes in both wild type cells and cells lacking Taz1. However, experiments to identify the mechanism of this exclusion failed, prompting our re-evaluation of H4K20me2 levels at telomeric chromatin. In this short report, we used an extensive series of controls to identify an antibody specific for the H4K20me2 modification and show that the level of this modification is the same at telomeres and internal loci in both wild type cells and those lacking Taz1. Consequently, telomeres must block activation of the DNA Damage Response by another mechanism that remains to be determined.

Model organisms such as budding yeast, worms and flies have proven instrumental in the discovery of genetic determinants of aging, and the fission yeast Schizosaccharomyces pombe is a promising new system for these studies. We devised an approach to directly select for long-lived S. pombe mutants from a random DNA insertion library. Each insertion mutation bears a unique sequence tag called a bar code that allows one to determine the proportion of an individual mutant in a culture containing thousands of different mutants. Aging these mutants in culture allowed identification of a long-lived mutant bearing an insertion mutation in the cyclin gene clg1(+). Clg1p, like Pas1p, physically associates with the cyclin-dependent kinase Pef1p. We identified a third Pef1p cyclin, Psl1p, and found that only loss of Clg1p or Pef1p extended lifespan. Genetic and co-immunoprecipitation results indicate that Pef1p controls lifespan through the downstream protein kinase Cek1p. While Pef1p is conserved as Pho85p in Saccharomyces cerevisiae, and as cdk5 in humans, genome-wide searches for lifespan regulators in S. cerevisiae have never identified Pho85p. Thus, the S. pombe system can be used to identify novel, evolutionarily conserved lifespan extending mutations, and our results suggest a potential role for mammalian cdk5 as a lifespan regulator.

Purpose: Opioid pain medication is most commonly prescribed after distal radius fracture fixation, and there is high variability in the quantity and duration prescribed. Comorbidities, including substance use and depression, have been associated with higher consumption habits, and increased sizes of postoperative opioid prescriptions have been previously linked to an increasing risk of chronic opioid use and opioid use disorder. The purpose of this study was to investigate opioid prescription patterns after distal radius fracture fixation and identify patient-specific risk factors associated with increased opioid prescription refills., Methods: A retrospective review of 34,629 opioid-naïve patients was conducted using the IBM MarketScan database. The database was queried to identify patient records from January 2009 to December 2017. Demographic, comorbidity, complication data, and prescription pharmacy claims were analyzed. Patients were sorted according to the duration of postoperative prescription refills of opioid pain medication., Results: Seventy-three percent of the patients required no additional refills outside the perioperative window. Twenty percent required additional refill prescriptions, and 6.4% of patients continued to fill the opioid medication beyond 6 months after surgery. Multiple factors increased the risk of increased opioid use, including medical and surgical complications, substance use, diabetes, cardiovascular disease, and obesity. Patients with a longer duration of opioid use after surgery had higher rates of medical and surgical complications. Perioperative prescription quantities were 62.9, 78.6, and 83.3 tablets for no refill, refill (<6M), and prolonged-use groups (>6M), respectively., Conclusions: Patients who underwent distal radius fracture fixation were at greater odds for prolonged opioid use after surgery in the presence of comorbid cardiovascular, renal, metabolic, and mental health illnesses and postoperative medical and surgical complications. A greater understanding of patient-specific factors for prolonged opioid consumption after distal radius fracture fixation can help providers identify at-risk patients who would benefit from a tailored approach to counseling and multimodal pain management. Patients should be educated on these risks associated with their surgery and be provided with alternative medical options and health care resources to optimize pain control and reduce their need for opioid medication as their primary tool for pain relief., Type of Study/level of Evidence: Therapeutic III., (© 2023 The Authors.)

Introduction: Carpal tunnel syndrome and ulnar nerve compression at the elbow (e.g., cubital tunnel syndrome) are the most common upper extremity compressive neuropa- thies treated by hand surgeons. The aim of this study was to determine demographic factors and comorbidities that can help predict those patients most likely to undergo concurrent release of both the carpal tunnel and ulnar nerve at the elbow. We hypothesized that certain comorbidities, such as diabetes, would be associated with an increased risk for the necessity of concomitant procedures., Methods: Using Truven Marketscan® database, all patients who underwent carpal tunnel release were identified from 2010 to 2017 using Current Procedural Terminology (CPT) codes. Patients were only included if they had continuous enrollment in the database for 12 months preoperatively. Preoperative comorbidities and concurrent procedures were collected us- ing CPT and ICD-9 and 10 codes. Patients who underwent simultaneous carpal tunnel and ulnar nerve at the elbow release on the same day were compared to those patients who underwent carpal tunnel release alone. Additionally, patients who underwent either procedure initially and then went on to have the other procedure at a later date were compared. Univariate analysis and binomial logistic regression were performed to assess the contribution of patient demographics and comorbidities on the necessity of simultaneous release., Results: 259,574 patients underwent carpal tunnel release surgery and were included in the study. 24,401 (7.9%) of pa- tients also underwent simultaneous ulnar nerve release at the elbow on the same day. Significant risk factors associated with the need for simultaneous release, were male gender [(Odds Ratio (OR): 2.05, Confidence Interval (CI): 2.00-2.11, p < 0.001)], chronic pain (OR: 1.78, CI: 1.68-1.87, p < 0.001), diabetes (OR: 1.29, CI: 1.25-1.33, p < 0.001), history of al- coholism (OR: 1.23, CI: 1.10-1.38, p < 0.001), chronic renal disease (OR: 1.26, CI: 1.18-1.34, p < 0.001), tobacco use (OR: 1.49, CI: 1.42-1.56, p < 0.001), and patients with congestive heart failure (OR: 1.26, CI: 1.17-1.35, p < 0.001). Patients with consumer driven health plans and high deductible health plans (HDHP) were 1.5 times more likely to have simultane- ous release compared to those with comprehensive plans (OR: 1.46, CI: 1.37-1.56, p < 0.001; OR: 1.45, CI: 1.34-1.57, p < 0.001; respectively). For necessity of subsequent carpal or ulnar nerve release after either primary procedure, patients with a minimum of 3 years enrollment in the database were analyzed. Of the 113,505 patients who underwent initial carpal tunnel release, 1,746 (1.5%) went on to undergo release of the ulnar nerve at the elbow. Of the 12,673 patients who had initial ulnar nerve releases at the elbow, 721 (5.7%) required additional release of the carpal tunnel., Conclusion: Identification of patient demographic factors and comorbidities that can help predict the likelihood of si- multaneous release of both the carpal tunnel and ulnar nerve at the elbow can help direct management of these patients. Combining the two procedures can help save resources, minimize patient burden, and help reduce excess health care utilization.

The purpose of this paper is to summarize the need, feasibility, safety, legality, and ethical perspectives of pacemaker reutilization in low- and middle-income countries (LMICs). It will also describe, in-depth, Project My Heart Your Heart (PMHYH) as a model for pacemaker reuse in LMICs. The primary source of the discussion points in this paper is a collection of 14 publications produced by the research team at the University of Michigan and its collaborative partners. The need for pacemaker reutilization in LMICs is evident. Numerous studies show that the concept of pacemaker reutilization in LMICs is feasible. Infection and device malfunction are the main concerns in regard to pacemaker reutilization, yet many studies have shown that pacemaker reuse is not associated with increased infection risk or higher mortality compared with new device implantation. Under the right circumstances, the ethical and legal bases for pacemaker reutilization are supported. PMHYH is a proof of concept pacemaker donation initiative that has allowed funeral home and crematory directors to send explanted devices to an academic center for evaluation and re-sterilization before donation to underserved patients in LMICs. The time is now to pursue large-scale studies and trials of pacemaker reuse for the betterment of society. PMHYH is leading the way in the effort and is poised to conduct a prospective randomized, non-inferiority, multicenter study to confirm the clinical efficacy and safety of pacemaker reuse, for clinical and legal support., Competing Interests: Conflict-of-interest statement: All the authors declare they have no competing interests.

Objective: Since post-traumatic stress disorder (PTSD) is common after military deployment and affects both military service members and their families, we sought to both improve PTSD-related knowledge of military family members and to foster actions to help service members with their symptoms., Methods: Focus groups were conducted with military family members and their feedback was incorporated into an educational Web site to improve family members' knowledge of PTSD. We pilot-tested the site and a 25-item questionnaire, then used it to assess the knowledge of 497 family members before and after their use of the Web site., Results: Use of this educational Web site improved military family members' PTSD-related knowledge on a 25-item test, with an increase from a mean 13.9 correct responses beforehand to 18.7 after Web site use (p < 0.001; effect size 1.2). In addition, 217 family members returned to the site > or =10 days after their initial visit; 57% had taken actions such as discussing the service member's symptoms with them or persuading them to get medical attention, and 82 to 95% of them believed their actions to be beneficial., Conclusion: A Web-based intervention can both improve PTSD-related knowledge and foster behavioral changes in military family members.

Objective: To describe an outbreak of serious nosocomial Burkholderia cepacia infections occurring after transrectal prostate biopsy associated with ultrasound gel intrinsically contaminated with paraben-degrading microorganisms., Methods: A retrospective chart review prompted by a blood culture isolate of B. cepacia. Identification of microorganisms in ultrasound gel in two Canadian centers and characterization by pulsed-field gel electrophoresis and assays for paraben degradation., Setting: Two Canadian university-affiliated, tertiary-care centers in Newfoundland and Alberta., Results: Six serious B. cepacia infections were identified at the two centers. Isolates of B. cepacia recovered from the blood of patients from both centers and the ultrasound gel used during the procedures were identical, confirming intrinsic contamination. Strains of Enterobacter cloacae isolated from ultrasound gel at the two centers were also identical. The ability to degrade parabens was proven for both B. cepacia and E. cloacae strains recovered from the ultrasound gel., Conclusions: Ultrasound gel is a potential source of infection. Contamination occurs at the time of manufacture, with organisms that degrade parabens, which are commonly used as stabilizing agents. There are far-reaching implications for the infection control community.

In the field of rheumatology, conventional diagnostic methods permit the detection only of advanced stages of the disease, which is at odds with the current clinical demand for the early diagnosis of inflammatory rheumatic diseases. Prompted by current needs, we developed a finger joint phantom that enables the optical and geometrical simulation of an early stage of rheumatoid arthritis (RA). The results presented here form the experimental basis for an evaluation of new RA diagnostic systems based on near infrared light. The early stage of RA is characterised mainly by a vigorous proliferation of the synovial membrane and clouding of the synovial fluid. Using a double-integrating-sphere technique, the absorption and scattering coefficients (mua, mus') are experimentally determined for healthy and pathologically altered synovial fluid and capsule tissue. Using a variable mixture of Intralipid Indian ink and water as a scattering/absorption medium, the optical properties of skin, synovial fluid or capsule can be selected individually. Since the optical and geometrical properties of bone tissue remain constant in early-stage RA, a solid material is used for its simulation. Using the finger joint phantom described herein, the optical properties of joint regions can be adjusted specifically, enabling an evaluation of their effects on an optical signal--for example, during fluorography--and the investigation of these effects for diagnostically useful information. The experimental foundation for the development of a new optical system for the early diagnosis of RA has now been laid.

We have developed an in vivo model for chronic evaluation of prosthetic heart valves using juvenile domestic sheep. This report summarizes the results of a study conducted to assess a new bileaflet prosthetic valve. Nine juvenile sheep underwent mitral valve replacement using standard cardiopulmonary bypass techniques including mild hemodilution, systemic hypothermia, and cold fibrillatory arrest. The average time on cardiopulmonary bypass was 57 min. There were no surgical or anesthetic complications. Two (22%) early deaths occurred due to prosthetic annular size disproportion (1) and preexisting pneumonitis (1); postmortem examination of both implanted devices revealed normal function. The remaining seven animals (78%) remained clinically well and underwent left and right heart catheterization, angiography, and sacrifice after the 150th postoperative day. Left ventriculograms demonstrated normal valve function in all cases. The average mitral transvalvular gradient, as determined by simultaneous pulmonary capillary wedge and left ventricular and diastolic pressure, was 5.4 mm Hg. Thus we have developed a new in vivo model that provides a successful model for chronic evaluation of prosthetic valves using a sheep model. There are several features contributing to the success of our model. First, to decrease the possibility of bacteremia and seeding of the prosthesis, a single incision is used and intraoperative monitoring lines minimized. Second, we use a short cardiopulmonary bypass run (range 52-62 min), with no period of ischemia. Third, fresh sheep blood is transfused immediately following bypass to prevent anemia. Fourth, gastric decompression is used to prevent ruminal bloating, with the resulting vena caval compression that decreases blood return while on bypass.

Sublethal doses of organophosphate anticholinesterases cause acute pancreatitis in dogs within 2 h. In vitro studies using canine pancreatic fragments have also demonstrated that the peak of amylase release in response to acetylcholine is shifted far to the left after incubation with the organophosphates echothiophate (10(-4) M) or tetraisopropyl pyrophosphoramide (iso-OMPA) (10(-3) M), indicating an increased sensitivity of response. The present in vitro study examined whether there was also an increased susceptibility to acinar cell damage at the electron microscopic level after acetylcholine or cholecystokinin. Minced pieces of whole fresh canine pancreas 2-3 mm in size were placed in buffered Eagle's solution and gassed with 100% O2. After pretreatment 1 h with echothiophate or iso-OMPA, they were then incubated with acetylcholine (10(-5) M). Other tissues preincubated with echothiophate were stimulated with cholecystokinin (10(-9) M). These are submaximal doses for untreated canine pancreatic fragments. After acetylcholine and echothiophate or acetylcholine and iso-OMPA, there was extensive acinar damage with the appearance of large vacuoles and lakes, and interstitial edema. There was evidence of intense supramaximal stimulation and lateral exocytosis. Similar destructive changes were seen after echothiophate and cholecystokinin. In control sections from tissues stimulated with acetylcholine (10(-5) M) or cholecystokinin (10(-9) M, there were lumenal exocytotic patterns typical of submaximal stimulation. Other controls, organophosphate alone and unstimulated basal conditions, showed only minor changes. It is concluded that the increased sensitivity to acetylcholine after organophosphate incubation correlates with an increased susceptibility to acinar ultrastructural damage from acetylcholine and cholecystokinin.

We have studied the potential use of immunotoxins (ITs) for therapeutic treatment of human tumors in an experimental model of human neoplasia. We tested intact ricin IT for its antitumor activity against established tumors. CEM, a human T-cell leukemia line expressing an Mr 67,000 cell surface antigen, and Daudi, a human B-cell lymphoma line which does not express the antigen, were found to be consistently tumorigenic in nude mice. ITs were synthesized using T101, a high-affinity monoclonal antibody reacting with the Mr 67,000 protein determinant and intact ricin. We have shown for the first time that established CEM solid tumors in nude mice will regress following intratumoral injection of T101-ricin IT, while Daudi tumors will not. Selective activity of T101-ricin is dependent on systemic i.v. administration of lactose and local intratumoral injection of the T101-ricin IT with lactose. Intact ricin ITs require the presence of lactose to block native ricin binding and render them antigen specific when linked to monoclonal antibody. Killing of target was cell specific since (a) nonspecific (irrelevant) ITs did not cause the regression of CEM tumors, and (b) injection of large amounts of free T101 antibody prior to T101-ricin IT blocked antitumor activity. Selectivity was not absolute, since regression occurred in one of six animals given irrelevant IT, and blocking was observed in two of four mice. Intratumoral IT treatment with 1 or 2 micrograms of T101-ricin IT plus lactose was not harmful to mice in contrast to intratumoral ricin treatment, which killed all treated tumor-bearing mice at a dose of 0.3 micrograms. Without i.v. injection of lactose, intratumoral injection of T101-ricin IT was also effective in eliminating established tumors. However, this treatment did not result in the selective elimination of tumor, since Daudi tumors also regressed following T101-ricin IT treatment. IT, made with ricin A chain only (T101-A chain IT), was also tested against established CEM tumors. We found that high dosages of T101-A chain IT did not destroy CEM tumors when injected intratumorally, even in the presence of activating agents such as NH4Cl or the carboxylic ionophore X-537 A. In contrast, in vitro experiments demonstrated that T101-A chain IT plus activating agents had potent and selective cytotoxic effect against CEM cells. We conclude that ITs are specifically toxic to established tumors. Although selectivity is not absolute, ITs exhibit potential as a new class of antitumor reagents.

The internal structure of the epidermal Langerhans' cell granule (LCG) was studied with optical transforms of electron micrographs representing 3 planes of sectioning. Its "limiting membrane" exhibited linear discontinuity with a periodicity of about 11 nm similar to the structural repeats of the core (10.8 mm) in both the "outer" and the "internal leaflets". The average thickness of the nonvesicular part of the LCG was 55.7 nm. Disarray present in the optical diffractograms was incompatible with crystallinic or paracrystallinic orderliness of the periodic structures in the LCG. The structure appeared as an assembly of 4 sheets of roughly hexagonally packed particles: The stacked particles of 2 sheets in orthogonal contact forming the core (13.2 nm) were separated by an intermediate space (2.7 nm) from the single sheet of the outer layer and staggered by one-half the particle diameter on cross-sections. The validity of this model was inferred from the similarity of optical transforms of model structures.

Histological changes which developed after percutaneous transluminal angioplasty in normal and atherosclerotic rabbit aortas were correlated with balloon size and inflation time. In normal rabbits, progressive changes were observed in the intima and media with increasing balloon size and inflation time. The atherosclerotic aortas exhibited unpredictable fragility, with limited correlation between histological changes, balloon size, and inflation time, attributable mainly to the distribution and thickness of plaques. In atherosclerotic vessels, the mechanism of angioplasty consisted of plaque dehiscence and fracture, followed by overstretching of the plaque-free wall segments. No plaque compression was observed.

Detailed enzyme kinetic parameters of the reactions catalyzed by the two 17beta-hydroxysteroid dehydrogenases (17beta-HSD), which were solubilized from the microsomes of human placenta by treatment with phospholipase A, followed by enrichment and separation were determined. Both enzymes are strictly substrate specific. The most active substrate of one of the 17beta-HSD (fraction A) is estradiol-17beta, the other 17beta-HSD (fraction B) is sensitive to testosterone. Both NAD and NADP can serve as hydrogen transferring coenzymes, the latter giving about one-third of the initial rate of the former. With respect to the influence of temperature, different buffers and pH values, Michaelis constants (Km) with estradiol-17beta and testosterone as substrates, the solubilized and separated microsomal 17beta-HSD behave like those isolated from the cytoplasmic fraction. The two 17beta-HSD, after solubilization from the microsomal fraction of human placenta, enrichment and separation from each other, show only a little activity for the transfer of hydrogen between C17 of estradiol-17beta and C17 of androstenedione. On the other hand, intact microsomes and an integrated system prepared by recombination of the 17beta-enzymes by preincubation in phosphate buffer are able to catalyse very actively the transfer of hydrogen between estradiol-17beta and androstenedione. The effect of temperature and time on the recombination of the two enriched and separated microsomal enzyme activities and the determination of the pH-optimum of the hydrogen transfer reaction are described. Finally it is proposed that the hydrogen transfer between steroid hormones represents an aspect of the true reaction mechanism of steroid hormones: Steroid hormones function as hydrogen transferring coenzymes by forming part of a chain of hydrogen carriers.

The organophosphate insecticide Diazinon has been reported to cause acute pancreatitis in dogs. Based on histochemical examination of the acinar tissue, it was suggested that pancreatic tissue-fixed butyrylcholinesterase (BuChE) is the target enzyme of organophosphate toxicity. To further evaluate this theory, we exposed dogs, cats, and guinea pigs to a single sublethal dose of the organophosphate insecticide Diazinon (75 mg/kg). In cats, which lack pancreatic BuChE, no pathological changes occurred after two, three, and six hours, whereas in the guinea pigs as in dogs, both having abundant pancreatic BuChE, vacuolization of the acinar cells, interstitial edema and vasculitis indicate acute edematous pancreatitis as early as two hours. Atropine pretreatment (0.2 mg/kg) gave complete protection against pancreatitis. It was concluded that inhibition of pancreatic BuChe leads to cholinergic hyperstimulation of the acinar cell, which results in acute pancreatitis, and that pancreatic BuChE is essential for dogs and guinea pigs to downregulate cholinergic excitation. The insecticide pancreatitis model is considered a simple, non-invasive, reproducible, and cheap and useful method to evaluate early changes and methods of treatment in acute pancreatitis. Pancreatitis in humans has also been reported after accidental insecticide exposure.

Polioencephalomalacia similar to that in domestic ruminants was diagnosed in two wild white-tailed deer (Odocoileus virginianus) with abnormal behaviour in Saskatchewan.

Potency testing of FMD vaccines by a three-point method was elaborated. Mice myotropic FMD virus was used as challenge virus. With this test the immunogenicity of FMD vaccines based on BHK, calf kidney or swine kidney was examined. The results are reproducible and allow quantification of the antigenic value of FMD vaccines within statistical limits.

Acute myocardial necrosis was produced in 27 anesthetized dogs by repetitive DC 75 joule shock delivered with one electrode in the left ventricular cavity and the other on the left chest wall. A total of 1 shock/kg body weight delivered at 10 sec intervals resulted in discrete anterior wall necrosis of 7% to 31% (mean, 17.6%) of the mass of left ventricular myocardium. After some transient bradycardia, normal sinus rhythm was restored. Depression of left ventricular function 15 min after shock (rise in LVEDP from 4.0 +/- 1.5 to 17 +/- 2 mm Hg and fall in cardiac output from 2.29 +/- 0.24 to 1.82 +/- 0.12 L/min) recovered only slightly during the ensuing 2 hr. A significant correlation (r=0.85) was observed between the LVEDP at 2 hr after shock and the extent of necrosis determined histochemically and histologically at the time of sacrifice 3 hr after shock. Thus, in this form of acute myocardial damage, pump dysfunction is closely related to the area of necrosis.

Fatal myopathy similar to "capture myopathy" described for African game was diagnosed in a wild white-tailed deer. Clinical signs included depression, inability to rise or stand, and myoglobinuria. Values for serum creatine phosphokinase, glutamic oxaloacetic transaminase, and blood urea nitrogen were high. The deer died 42 hours after capture. At necropsy the muscles of the limbs had a waxy, "cooked" appearance and the kidneys were brown. Microscopic findings included severe degeneration and fragmentation of skeletal muscle fibers, nephrosis, centrilobular hepatic necrosis, myocardial degeneration, and anoxic neuronal degeneration.

The effects of pancreatic intraductal infusions of the surface active pancreatic ductogram enhancing agent, polyoxyethylene hydrogenated castor oil, were studied in the dog. Moderately high pressure retrograde infusions of 5 per cent polyoxyethylene hydrogenated castor oil into the main pancreatic duct resulted in pancreatitis-like changes significantly greater than those seen in the saline solution control group. These changes persisted despite buffering of the agent to physiologic pH and the elimination of nonphysiologically high pressure by direct ductal perfusion. Similar inflammatory changes were associated with ductal perfusion using oleic and, to a lesser degree, ricinoleic-fatty acids at concentrations of 10(-4) molar sufficient to account for the titratable acidity of 5 per cent polyoxyethylene hydrogenated castor oil. It is postulated that residual-free fatty acids may play some role in polyoxyethylene hydrogenated castor oil related toxicity. The surface active properties of the agent may also be involved. Caution and further research are recommended prior to widespread use of the agent in endoscopic retrograde pancreatography.

Degenerative lesions were found in the skeletal system of 20 to 128 white-tailed deer (Odocoileus virginianus) examined. Similar changes were found in an aged male moose (Alces alces). Arthropathy involving the stifle joint was present in 60% (15/25) of male deer 4 years of age or older, and in 16.7% (4/25) of females in the same age range. Vertebral osteophytes were not found in any of 62 female deer, nor in male deer less than 6 years of age, but were present in 50% (7/14) of males 6 year of age or older. The possible etiology and significance of the conditions are discussed.

Treatment of human placenta microsomes with phospholipase A or D inhibits the 17beta-hydroxysteroid dehydrogenase (17beta-HSD) activity, parallel with the hydrolysis of membrane phospholipids. The 17beta-HSD activity of phospholipase treated microsomes is reactivated by synthetic phospholipids. The distribution of 17beta-HSD activity in subfractions of original microsomes and of phospholipase treated microsomes obtained by zonal centrifugation was studied. Solubilization of the microsomal 17beta-HSD was achieved by phospholipase A treatment. Two 17beta-HSD were solubilized from human placenta microsomes by phospholipase A treatment and were further purified by ammonium sulphate precipitation, gel filtration on BioGel A-0.5 m, DEAE-Sephadex chromatography and by isoelectric focusing. The enzymes were purified 25.8 and 17.4 times. The isoelectric points and molecular weights of the two 17beta-HSD were determined. Both enzymes are of a 17beta-HSD type. One of the 17beta-HSD, however, was sensitive to estradiol-17beta, the other to testosterone. The question of whether the two enzymes constitute a monomer and a dimer of the same 17beta-HSD or are completely different enzymes, is discussed.

The trematode Metorchis conjunctus (Cobbold, 1860) was found in seven of 211 wolves from Saskatchewan which were examined between 1976 and 1983. The parasite caused cholangiohepatitis with periductular fibrosis in the liver of all the wolves, and chronic inflammation and fibrosis of the pancreas in two animals. The wolves with pancreatic involvement were emaciated. Five of the seven infected wolves were from one local area, and three of these were from a pack known to consume fish.