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The reproducibility of various procedures for the noninvasive assessment of the skeleton in dogs has been measured. In one animal, dual photon measurements of bone mineral mass were made in the whole body, the lumbar spine, and the proximal femur on 10 occasions during a 15-week period. In two other dogs, repeat measurements of Tc-99m imidodiphosphate (IDP) retention were made. For the total body and the proximal femur, the reproducibilities were 2 and 2.5%, respectively. The reproducibility of the lumbar spine was approximately 10% and was influenced by the variable fraction of the posterior spinous processes included in the measurement. The reproducibility of IDP retention measurements was not established. It was about 8% when all 10 measurements were considered but fell to 1.5% when three consecutive measurements were excluded. Dual photon measurements of the whole body and the proximal femur can be used to assess bone mass changes in the canine skeleton. [ABSTRACT FROM AUTHOR]

Anti-NMDAR encephalitis is a newly characterized syndrome with a progressive, predictable clinical course and the possibility of effective treatment. Accurate and timely diagnosis is critical to selection and implementation of treatments, and optimal patient outcomes. Outcomes are improved with early diagnosis via indirect immunofluorescence or cell-based assays, and the rapid and appropriate administration of immunosuppressant and anti-psychotic therapies. Three possible scenarios accounting for the immunopathogenesis of anti-NMDAR encephalitis are presented, with the most probable one being that of paraneoplastic autoimmunity. Future efforts in this disorder should focus on elucidating the mechanisms that contribute to initiation of this antibody response, as well as exploring the role of tumors, infectious triggers and immune-reactivation. Finally, accessible tools need to be developed that allow for reliable identification of specific antibody markers against synaptic proteins., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The inadvertent extravasation of anticancer drugs in clinical use may result in the development of indolent lesions at the site of injection. Investigation of this phenomenon in Hartley guinea pigs showed that the pathogenesis was based on direct tissue toxicity and not on sensitization. The risk of a serious reaction appeared to be related to the localization of the injurious agent within the dermis rather than at the subcutaneous site.

A subacute toxicity study on 99m Tc stannous glucoheptonate was performed with rats, dogs and rabbits, injected intravenously at ten to 100 times the human dose on a body weight basis. There were no abnormalities in the clinical status of any of the animals. No changes were found in urinalysis, blood chemistry or hematology in the rabbit nor in gross examination, renal histology or bone marrow smears in the rats and rabbits. Hepatic histology was also done. A focal area of necrosis in a liver of one rabbit that had been injected with 100 times the human dose was observed using light microscopy. Examination by electron microscopy in another group of rats and rabbits was prompted by the observation of that lesion. This revealed vacuolated and dilated smooth endoplasmic reticulum and degranulated and vesiculated rough endoplasmic reticulum in all the test livers. X-ray microanalysis indicates that the ultrastructural changes are linked to the deposition of tin.

Test doses (0.5 ml) of the perfluorochemical blood substitute Fluosol-DA causes pulmonary hypertension in some patients. To investigate this phenomenon we infused Fluosol-DA into unanesthetized sheep with chronic vascular catheters on ten occasions. In six of these experiments lung lymph flow was measured. Since other fluorochemical blood substitutes alter the coagulation cascade we also sampled blood to perform coagulation screening tests and look for evidence of thrombin generation as assessed by the survival of 125I labelled sheep fibrinogen. Test doses (0.5 ml) of Fluosol-DA resulted in transient but marked pulmonary hypertension in nine of ten experiments (17 +/- 1.2 SE to 43 +/- 3.9 SE torr). Cardiac output decreased by an average of 30%, and lung lymph flow transiently increased without a change in the lymph to plasma protein concentration (L/P) ratio in five of six experiments. When 50 ml of Fluosol-DA was administered one hour later the pulmonary hypertension was more prolonged but less severe (18 +/- 1.0 SE to 34 +/- 3.2 SE torr). Lymph flow again increased without a change in the L/P ratio for protein. The activated partial thromboplastin and prothrombin times, and survival in plasma of 125I labelled sheep fibrinogen were unaffected by administration of Fluosol-DA. We conclude that Fluosol-DA causes pulmonary hypertension in sheep and increases lung lymph flow. This results from vasoconstriction of the pulmonary vessels and subsequent recruitment of the pulmonary microvasculature and not from thromboembolic phenomena.

In previous experiments it was shown that repeated mechanical or immunologic injury to the arterial intima of normally fed rabbits induced lesions morphologically identical with human atherosclerosis. These regressed in size and lipid content when the injury stimulus was removed. By contrast, repeated injury directed to removal of only the endothelial layer induced lesions in which lipid accumulated in areas of endothelial regeneration and increased with time. In the present report the lesions associated with multiple and with a single episode of endothelial removal, using a Fogarty balloon catheter, are compared. Lipid accumulates in areas of endothelial regrowth following one endothelial injury and is similar in amount to that at comparable time intervals following the first of multiple balloon removals of the endothelium. There is much more lipid in areas of endothelial regrowth than in areas that remain uncovered by endothelium, the lipid tends to increase with time, and there is more lipid in the abdominal aortic than in the thoracic aortic lesions. A correlation was found between lipid content and thickness of lesions, especially in response to multiple removals of the endothelium. Multiple removals resulted in thicker lesions than a single injury. There appeared to be a positive relationship between the level of blood cholesterol and the amount of lipid deposited in areas of endothelial regrowth. This is consistent with trapping of low density lipoprotein by glycosaminoglycans in the neointima covered by regenerated endothelium.

Tissue wet weight as well as total protein content, 5'-nucleotidase activity, alkaline phosphatase activity and Ca2+ accumulation associated with a plasma membrane fraction isolated from spontaneous hypertensive rats (SHR) and rats with deoxycorticosterone (DOC) induced hypertension were investigated. Enhanced alkaline phosphatase activity and reduced ATP-dependent Ca2+ accumulation preceded the development of hypertension in SHR and these effects were reversed by DOC withdrawal followed by lowering of blood pressure in DOC hypertension. Increased arterial tissue wet weight and 5'-nucleotidase occurred only at the later stage of hypertension in SHR and the increased tissue wet weight was not reversed by DOC withdrawal in DOC hypertension. These observations suggest that enhanced alkaline phosphatase and reduced ATP-dependent Ca2+ uptake may play a significant role in initiating hypertension, while increased arterial wet weight and 5'-nucleotidase activities may participate in the maintenance of hypertension.

The use of autogenous vein as an arterial substitute has been advocated for many years. Methods of harvesting generally cause spasm of the vein and it has been shown that preventing the spasm by applying papaverine improves long-term patency. The present study was undertaken to see if the reported long-term patency of such grafts was associated with improved short-term appearance of the venous endothelium as viewed with the scanning electron microscope. Two groups of dogs were studied; those sacrificed at 3 hours and those at 24 hours after replacing excised segments of the carotid and femoral arteries with cephalic veins. One of the veins was removed in the standard manner allowing spasm followed by distension back to its pre-spasm state; in the other, spasm was prevented by the topical application of papaverine before removal. The study shows that venous endothelial integrity is preserved by the use of papaverine and this improved appearance of the endothelium persists for the first 24 hours after insertion into an arterial milieu. But the study also demonstrated that there was extensive activity of polymorphonuclear leukocytes associated with the endothelium in the early hours after arterialization and that they appeared to have a deleterious effect on the endothelium.

We investigated the effects of a partial compared to a complete thrombotic occlusion of the left anterior descending coronary artery in dogs. A completely occlusive thrombus was associated with a full thickness myocardial infarction. Mural thrombus was associated with focal areas of myocardial injury, mainly subendocardial in location. The findings are compatible with the concept that mural thrombus can give rise to platelet or platelet-fibrin emboli in the microcirculation which cause focal areas of ischemic damage. This pathogenesis was further explored using a thrombogenic wire placed in the left anterior descending coronary artery by indirect technique. Five of 10 dogs had developed a completely occlusive thrombus, whereas five had a mural thrombus at death, which occurred within 2 days. Three of the five dogs with mural thrombus had focal ischemic myocardial damage and platelet-fibrin thrombi; the other two that died early showed only platelet fibrin masses in the microcirculation. When platelets were labeled with 111Indium, there was increased radioactivity in the territory of the myocardium served by the artery containing a developing thrombus.

In order to determine whether the ovarian follicles of the domestic cat which normally ovulates following copulation, were similar to those of the rabbit steroidogenically, the following experiments were carried out. Follicles were dissected out of ovaries from nine estrous cats throughout the year and incubated in medium alone or with luteinizing hormone (LH) or human chorionic gonadotropin (HCG). Media were removed every 15 min and stored frozen until analyzed for testosterone using established radioimmunoassay procedures. Although LH and HCG caused slight increases in testosterone production the amounts produced were much less than that produced by rabbit follicles under identical conditions. However, when follicles were incubated for a total of 8 h without removal of media, marked changes in testosterone and estradiol production occurred. These data suggest that the ovarian follicles of the estrous cat are steroidogenically active.

Intraperitoneal (IP) administration of the glutaramic acid derivative proglumide inhibited satiety induced by all IP doses of cholecystokinin octapeptide (CCK-OP) in 3-hour food-deprived intact rats. Proglumide did not influence satiety when administered alone and did not inhibit satiety induced by IP glucagon. While proglumide did not inhibit satiety induced by low doses of IP bombesin, it partially and significantly inhibited the satiety effects produced by high doses of this peptide. Since bombesin is a known secretagogue for CCK in several species, these results indicate that while bombesin and CCK act independently to induce satiety, the effect induced by high doses of bombesin is mediated, in part, by the release of endogenous CCK or a structurally related peptide. Furthermore, these results illustrate that proglumide is a specific antagonist of CCK-induced satiety and is, therefore, a potentially useful tool for investigating the physiologic role of this peptide in the control of food intake.

To assess the effects of a gonadotropin-releasing hormone agonist, [D-Leu6,des-Gly10] luteinizing hormone-releasing hormone ethylamide, in ameliorating the damage caused by ionizing radiation, gonadotropin-releasing hormone agonist was administered to rats from day 22 to 37 of age in doses of 0.1, 0.4, and 1.0 microgram/day or vehicle and the rats were sacrificed on day 44 of age. There were no effects on estradiol, progesterone, luteinizing, or follicle-stimulating hormone, nor an effect on ovarian follicle numbers or development. In separate experiments, rats treated with gonadotropin-releasing hormone agonist in doses of 0.04, 0.1, 0.4, or 1.0 microgram/day were either irradiated or sham irradiated on day 30 and all groups sacrificed on day 44 of age. Irradiation produced a reduction in ovarian weight and an increase in ovarian follicular atresia. Pretreatment with the agonist prevented the reduction in ovarian weight and numbers of primordial and preantral follicles but not healthy or atretic antral follicles. Such putative radioprotection should be tested on actual reproductive performance.

We have validated a radiochemical technique for measuring the rate of secretion of plasma triglycerides from the liver and/or splanchnic region during the consumption of glucose under isotopic steady-state conditions. Values obtained with this technique correlated closely with those based on transhepatic or transsplanchnic chemical gradients (r = 0.95). Likewise, values for secretion of triglycerides obtained with the radiochemical technique correlated closely with those obtained for extrahepatic or extrasplanchnic triglyceride clearance. Values for mean net splanchnic and hepatic secretion of plasma triglyceride fatty acids, transported essentially in very low density lipoproteins, were 1.9 and 2.0 mumoles/min.kg body wt0.75, respectively, about one-half of the rate of transport of free fatty acids. However, the fraction of triglyceride fatty acids of plasma very low density lipoproteins that was derived from plasma free fatty acids averaged 9% and that derived from glucose, though increasing with time, reached only 2% after constant intravenous infusion of radioglucose for 5 hr. Porcine hepatic secretion of plasma triglycerides is large in the glucose-fed state, and the secreted triglyceride fatty acids evidently are derived from stored fat or glycon.

Mature dogs were vaccinated with a myxovirus vaccine. At this time, half of the dogs were also given a subcutaneous injection of levamisole hydrochloride (2.2 mg/kg). Blood platelets were counted daily. The dogs that had received only the vaccine showed, after 48 hours, a 48% decrease in platelets. Levamisole reduced the thrombocytopenia associated with myxovirus vaccination. Levamisole could have a protective effect on platelets by preventing their aggregation induced by viral neuraminidase.

The effects of radiation and chemotherapy on gonadal function are relevant to the morbidity induced by such treatments. Cyclophosphamide given i.p. to rats on Day 30 of age delayed vaginal opening, prevented vaginal cyclicity, and caused a reduction in serum estradiol and progesterone. Antral follicular atresia increased in a dose-dependent fashion in response to cyclophosphamide (0 mg/kg, 53.5%; 1 mg/kg, 67.3%; 50 mg/kg, 65.7%; 100 mg/kg, 73.9%; 150 mg/kg, 92.2%). Despite such alterations in ovarian function, serum gonadotrophins did not rise. The concurrent administration of 0, 20, 30, 40, 50, and 60 Gy of radiation to the exteriorized ovaries in rats receiving 50 mg/kg cyclophosphamide induced widespread loss of primordial, preantral, and healthy antral follicles associated with reduction in serum progesterone and estradiol. Such irradiation induced dose-related increases in serum follicle-stimulating hormone and luteinizing hormone. Parenteral cyclophosphamide and local irradiation appear to induce ovarian toxicity by different mechanisms.

Protein content, enzymatic activites and Ca2+ accumulation capacities were studied in plasma membrane fractions isolated from mesenteric arteries of rats made hypertensive by renal artery stenosis with and without contralateral nephrectomy, i.e., one-kidney, one clip (1-KHR) and two-kidney, one clip (2-KHR) hypertension, respectively. Both types of renovascular hypertension showed similar vascular plasma membrane abnormalities which included increased total protein contents, enhanced alkaline phosphatase activities and reduced ATP-dependent Ca2+ accumulation compared to control values. The altered alkaline phosphatase activity and ATP-dependent Ca2+ accumulation appeared to be associated with blood pressure elevation in both types of hypertension and may be related to the elevation of blood pressure insensitive to captopril (SQ 14,225) in 1-KHR and 2-KHR. These results are consistent with the current concept of biochemical abnormalities of arterial smooth muscle in the development ostem.

To study the efficacy of topically administered thrombin as an adjuvant in tubal microsurgery, 24 rabbits underwent a 1-cm resection and microsurgical anastomosis of both fallopian tubes and were randomized to either thrombin or cautery for hemostasis. Ovarian wedge biopsies were done on the left ovary. The animals were mated 4 to 5 weeks postoperatively with a buck of proven fertility. They were killed at 2 to 3 weeks' gestation to note the number of fetuses per patent tube and presence or absence of pelvic adhesions. There was no effect of topical thrombin on the crude pregnancy rate but it was associated with a marked reduction in the number of fetuses per patent tube, despite similar rates of pelvic adhesions between groups. Topically administered thrombin appeared to reduce fertility in this experimental model by an undefined mechanism.

This study compares the effects on intimal hyperplasia of different methods of manipulating a vein graft before using it as an arterial substitute. Grafts that were denuded of endothelium showed the most intimal hyperplasia, while those that were washed with saline, dilated with saline or crushed did not differ appreciably from each other with respect to the degree of intimal hyperplasia. The hyperplasia was well developed and stabilized at 3 weeks, which coincided with restoration of the endothelial surface. The similarity between the last three methods of graft manipulation suggests that minor endothelial disruption produced at the time of harvesting the vein is equalized after insertion of the vein into the arterial circulation.