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Biomedical subjects

C R Spillert

Publications and source records attributed to C R Spillert.

At least 55 records · Page 3Linked to original sources

Hypercoagulability in arterial disease.

Isolated human monocytes generate tissue factor when stimulated with endotoxin. Tissue factor generation provides a marker for activation of the monocyte and of the clotting system. Determination of the recalcification time of blood after incubation with endotoxin detects minute changes in coagulability. This clotting assay was utilized to assess the presence of a hypercoagulable state in patients with peripheral arterial occlusive disease when compared with healthy volunteers. Citrated blood was incubated with endotoxin for two hours, CaCl2 was added, and the recalcification time determined. Hypercoagulability was indicated by shortened recalcification time. The recalcification time +/- standard deviation for saline (control) and endotoxin-activated samples from 19 healthy volunteers was 6.55 +/- 0.8 and 5.69 +/- 0.7 minutes, respectively, whereas it was 4.93 +/- 1.2 and 4.55 +/- 0.9 minutes for 31 patients with peripheral arterial occlusive disease (p less than .001 for each). This hypercoagulable state can accentuate the arterial occlusive process in patients with peripheral vascular disease and may prove to be of diagnostic, therapeutic, and prognostic significance.

Arterial Occlusive Diseases↗

Prediction of clinical course in diabetes using a simple coagulation test.

Peripheral vascular complications in diabetic patients are extremely variable. It has been suggested that they are related, in part at least, to accelerated blood coagulation. However, a simple test to monitor these changes in coagulability has not been previously described. This article reports that a test in which citrated blood, when incubated with either saline (control) or with endotoxin (to activate the extrinsic pathway) and then subjected to the determination of the recalcification time, can detect minute changes in coagulability. This technique showed that the recalcification times of both saline and endotoxin-incubated blood samples were significantly shorter in a majority of diabetic patients than in controls. These studies substantiate the significant incidence of hypercoagulability in diabetics.

Adult↗

Assessment of monocyte function in breast disease.

Monocyte dysfunction has been reported in patients with cancer. The generation of a procoagulant tissue factor is a marker of the monocyte's activation. Since the only blood cell capable of generating tissue factor is the monocyte, the incubation of citrated blood with either saline (control) or endotoxin (monocyte activator) followed by determination of the recalcification time should yield a measure of monocyte activation. The recalcification times of the saline-incubated samples were similar for healthy women and those with cystic hyperplasia, but were significantly shortened in patients with breast cancer. The recalcification times of the endotoxin-activated samples were significantly shorter in patients with breast cancer than in those with cystic hyperplasia, which in turn was significantly shorter than in healthy women.

Adult↗

Procoagulant effect of aqueous humor on in vitro clotting of blood and plasma.

Fresh and previously frozen aqueous humor was found to shorten the recalcification time of both canine citrated blood and human citrated plasma. This state of accelerated coagulation was dose related and preliminary studies indicate that aqueous humor acts as a procoagulant rather than a thromboplastin-like substance.

Animals↗

Effect of a butter-rich diet on murine frostbite.

A simple reproducible, humane model for producing frostbite in rodents is desirable. We have developed such a model and have investigated the effects of a butter-rich diet on severe cold injury. Mice (25 +/- 2 g) were randomly divided into two groups (n = 10). One group was given a standard rodent diet and the other group a butter-enriched (25%) rodent diet for 1 month. Under pentobarbital sodium anesthesia the mice were placed in a plastic funnel with the stem removed so that the entire tail protruded. The tails were submerged in a freezing solution (-18 degrees C) for 8 min. The mice received no further treatment. Tail lengths were measured 2 weeks after freezing to determine the amount of tail surviving from cold injury after autoamputation. Mean tail lengths (cm +/- SD) for the two groups were as follows: butter-rich diet, 4.3 +/- 1.8; standard diet, 7.3 +/- 2.0 (P less than 0.002). A high saturated-fat diet has a deleterious effect in murine frostbite. This simple model can be employed to test various modalities in the treatment of frostbite.

Animals↗

Recalcification time in breast disease.

Hypercoagulability in malignant disease can be attributed, in part, to excess generation of tissue factor (thromboplastin) by the monocyte. Incubation of anticoagulated venous blood with endotoxin (a cellular activator) enables the generation of tissue factor by monocytes. The quantity of this procoagulant generated is determined by a simple recalcification time (a marker for cellular activation). Individuals with breast cancer have significantly shorter endotoxin-activated recalcification times than patients with cystic hyperplasia, who have, in turn, significantly reduced recalcification times when compared with those of healthy volunteers.

Adult↗

Alcohol increases mortality in murine head injury.

Head injury is a major factor in the mortality of traumatized patients, accounting for about 50 percent of the resulting fatalities. Alcohol intoxication is frequently (25 to 50 percent) associated with head injuries. This study was undertaken to investigate the effects of alcohol on head trauma in a standardized animal model. Swiss Webster mice (25 ± 2 g) were given intraperitoneally 0.2 mL of either saline or 50 percent ethanol in saline. Thirty minutes later, under light ether anesthesia, severe concussion was produced by dropping a 39.5-g lead weight from a height of 30 cm. The trauma was centered on the midskull by channeling the weight through a vertical tube, 1.2 cm in diameter. Animals were observed daily for eight days. Among the controls, 12 of 12 mice, (100 percent) survived for four days and 8 of 12 (67 percent) survived eight days. In the alcohol recipients, there were 10 of 21 survivors (48 percent) at four days and only one survivor (5 percent) at eight days. This study clearly demonstrates that alcohol increases the lethality of standardized head trauma in mice. The mechanism by which alcohol modifies the effects of craniocerebral trauma remains to be elucidated.

Alcoholic Intoxication↗

Beneficial effect of sulfamethoxazole and trimethoprim on accelerated coagulation.

We have shown that the drug combination of sulfamethoxazole and trimethoprim has a radio protective effect in mice. Since radiation injury is due in part to microvascular thrombosis produced by the release or action of thromboplastin, we evaluated the effect of these drugs individually on thromboplastin-accelerated coagulation. Sulfamethoxazole at a final concentration of 0.05 microgram/ml and trimethoprim at concentrations of 0.005 and 0.05 microgram/ml significantly prolonged the recalcification times of human plasma. Whether these drugs have an anticoagulant effect when employed clinically remains to be determined.

Anticoagulants↗

A peroxide-induced inflammation model for drug testing.

Peroxide-induced cellular injury is an important mediator of inflammation. Whether the injection of glucose oxidase (GO) with its generation of H2O2 may be utilized as an inflammatory model was studied. Anesthesized mice were injected in the right hind foot with either water or an equal volume of 10 or 100 units/ml GO. The animals were sacrificed at 1.5 or 24 hours post injection and both hind feet amputated and each foot weighed. Difference in weights for each animal's feet was called edema index (EI). GO produced significant increases in weight. The use of GO to produce inflammation may be useful in testing potential peroxide quenching agents.

Animals↗

Shortened endotoxin-activated clotting times in patients with carcinoma.

Isolated human monocytes generate tissue factor when stimulated with endotoxins. This tissue factor generation provides a convenient marker of monocyte activation. Furthermore, the only circulating blood cell capable of generating large quantities of tissue factor is the monocyte. Therefore, the addition of endotoxin to citrated blood, and the determination of the recalcification times after incubation, yields a measure of monocyte activation. In order to determine whether monocyte activation as measured by this technique varies between patients with carcinoma and healthy volunteers, recalcification times were evaluated. The recalcification time and range for 19 healthy volunteers (controls) was 6.55 min (5.3-8.5) for the saline incubated sample and 5.69 min (4.6-7.2) for the endotoxin-activated sample. The results for 13 patients with carcinoma are 4.81 min (3.3-6.3) for the former and 3.17 min (2.0-4.3) for the latter. These results show that the longest recalcification time with endotoxin incubation for patients with carcinoma was lower than the lowest recalcification time in the control group. Whether this simple test can be of use in the diagnosis and monitoring of patients with carcinomas is currently being investigated.

Adult↗

Current attitudes in the management of obstructive biliary tract disease.

The current attitudes of surgeons towards the management of obstructive biliary tract disease were assessed by analyzing the responses of general surgeons to a 20-item questionnaire. The responses indicate that ultrasound is the most favored initial diagnostic test for suspected choledocolithiasis. Ninety-nine per cent of the respondents always or almost always insert a T-tube following exploration of the common bile duct for stones. For patients with stone impacted at the ampulla of Vater, sphincterotomy with or without sphincteroplasty is recommended by 86 per cent of surgeons. However, differences are noted in the approach to management of malignant lesions in the biliary tract. For carcinoma of the head of the pancreas, at laparotomy, if the lesion is resectable, 59 per cent of the surgeons will perform a Whipple procedure, nine per cent a total pancreatectomy, and 28 per cent recommend bypass only. For unresectable carcinoma of the head of the pancreas, 73 per cent perform cholecystojejunostomy, and 26 per cent prefer choledocojejunostomy. In addition to the biliary bypass, only 57 per cent perform a gastric bypass routinely. The favored treatment (62%) for unresectable common bile duct tumors is an internal bypass. However, following bypass, only 45 per cent recommend further treatment with radiation and/or chemotherapy. Therefore, it appears that there is agreement on the treatment of biliary obstruction due to stones. Differences are noted, however, in the approach to the management of malignant disease.

Attitude of Health Personnel↗

Increased lethality of endotoxemia in murine frostbite.

Because frostbite (FB) is associated with increased intravascular coagulability, it is reasonable to assume that endotoxin, by enhancing platelet aggregation, will adversely affect FB. Swiss mice (25 +/- 2 g) were anesthetized, and the tails of the animals totally immersed in a freezing solution of equal volumes of ethylene glycol and water (-18 C) for 8 min. The tails were then thawed at room temperature (24 C). Half an hour after removal from the freezing solution, the animals were given either (Group A) 0.1 cc saline I.P. or (Group B) 0.1 mg E. coli endotoxin (055:B5; 1/3 LD50 dose) in 0.1 cc saline IP. A third group (Group C), was given the same dose of endotoxin but was not subjected to frostbite. Survivals in each group at 2 weeks were as follows: (A) 14/14 (100%), (B) 4/20 (20%), (C) 13/14 (93%). Using Fisher's exact test, A versus B P less than .001; B versus C P less than .001; A versus C NS. The data presented here emphasize the increased lethality of endotoxemia in murine FB.

Animals↗

Effect of splenectomy on acute inflammation.

It is becoming increasingly evident that platelets play a significant role in the inflammatory process. Heterogeneity has been demonstrated among platelets, and evidence has been presented that the spleen retains the youngest and hemostatically most effective platelets. The present study was designed to determine what effect splenectomy, by removing a special population of platelets, would have on acute inflammation as manifested by carrageenan-induced murine foot pad edema. Swiss white mice (25 +/- 2 g) were anesthetized and subjected to splenectomy (Group A, n = 13) or to celiotomy only (Group B, n = 15). One week later, carrageenan (0.1 cc of 1% solution) was injected into the right hind foot pad of each animal. The mice were killed 3.5 hr later, and both hind paws amputated at the tibio-tarsal joint and weighed individually. The change in weight of the experimental hind paw relative to control was expressed as edema index for each animal. The inflammatory reaction, as manifested by carrageenan edema, was significantly (P less than 0.001) decreased in those animals subjected to splenectomy. The mean edema index in Group A was 62.8 per cent compared to 80.9 per cent in Group B. The results of this study indicate that splenectomy decreases inflammation as manifested by carrageenan-induced edema. Splenectomy eliminates a population of platelets having greater functional capabilities than those found in the peripheral circulation and impairs the organism's ability to respond to injury.

Animals↗

Beneficial effects of ethanol on experimental burns.

Alcohol has been demonstrated to produce cutaneous vasodilation. The burn wound is characterized by a compromised microcirculation which is amenable to pharmacologic manipulation to improve the final outcome of the injury. Various agents including heparin, aspirin, nonsteroidal anti-inflammatory agents have been employed to maintain a patent microcirculatory bed. Ethanol has been used in the present study in a murine burn model as a vasodilator administered immediately preburn and post-burn. Preburn administration of ethanol significantly improved the mean burn severity at 48 hr compared to ethanol given post-burn. Ethanol, acting as a vasodilator, improves dermal circulation post-burn and reduces the overall extent of injury.

Animals↗

Paradoxical effect of burns in diabetic mice.

Since the microcirculation is impaired in diabetes and since burn injury is associated with microvascular thrombosis, the purpose of this study was to determine whether diabetes increases the severity of burns. Swiss white mice were made diabetic with alloxan, and control animals received saline. One week later, animals with over 2000 mg/dl urine sugar and the control animals were anesthetized and burned uniformly on the back with a steel disc at 100 C for 10 sec. At 24 hr, burn severity was evaluated on a scale of 0 to 4 using gross and microscopic criteria. The mean burn severity of the diabetic mice was 0.80 +/- .15 and that of the control mice was 3.22 +/- .09 at 24 hr (P less than 0.001.). At 5 days, the differences of the burn severity between the two groups were still significant, but 5/10 (50%) of the diabetic mice and none of the control mice died. In diabetic mice, through burn severity appears mild in the wound, the mortality is high. Therefore, the criteria for initial evaluation of the diabetic with burns need to be reassessed.

Alloxan↗

Thromboelastographic evaluation of mini-dose heparin in minor surgical procedures.

Five dogs weighing approximately 10 kg were anesthetized with pentobarbital sodium 30 mg/kg intravenously (IV) and an initial sample of blood was drawn by jugular venipuncture for control values of thromboelastography (TEG). Immediately after venipuncture, mini-dose heparin (80 units/kg) was administered subcutaneously. One hour later, 0.5 ml blood was obtained by (A) jugular venipuncture for TEG, and an indwelling catheter immediately introduced into a femoral vein by cut-down. Blood samples for TEG were obtained via cut-down at (B) 15 min (C) 30 min, and (D) 60 min after cut-down. Low-dose heparin had no effect on the hemostatic parameters as measured by TEG and did not prevent the accelerated coagulation associated with surgery.

Animals↗

Effect of surgery on tumor-induced accelerated coagulation in a rat carcinoma.

Accelerated coagulation detected by thromboelastography has been reported in early stages of tumor growth. The present investigation was conducted to determine the changes in tumor-induced accelerated coagulation following complete and partial resection of the tumor. Male Fisher rats were divided into four groups: (1) control, (2) tumor-bearing rats, (3) complete resection, (4) partial resection. In groups 2, 3, and 4 a 2-mm3 piece of squamous cell carcinoma (NCI 11095) was implanted subcutaneously in the left flank. Seven days later blood samples were obtained from the tumor and control groups and tested on a thromboelastograph to determine the effect of the tumor on the coagulation of the hosts. Six weeks following the initial tumor implantation a sham operation was performed on group 2, complete resection on group 3, and a partial resection on group 4. After a rest period of 3 weeks blood samples were obtained from the four groups of rats and tested on a thromboelastograph. The results indicate that there is a significant acceleration of coagulation in tumor-bearing animals. The effect of surgery on this tumor-induced phenomenon depends on the type of procedure performed. Complete resection returns the coagulation status toward normal whereas sham operation or a partial resection do not. In this tumor model, hypercoagulability of the blood, therefore, indicates the presence of residual tumor.

Animals↗