Biomedical subjects

T Adams

Publications and source records attributed to T Adams.

At least 91 records · Page 5Linked to original sources

PubMed1986

Dinitrotoluene isomer-specific enhancement of the expression of diethylnitrosamine-initiated hepatocyte foci.

Technical grade dinitrotoluene (TDNT) was shown to be a potent hepatocarcinogen in rats; however, ambiguous results were obtained from bioassays which evaluated 2,4-DNT, the principal isomer in the technical mixture. The present studies were designed to determine the relative hepatocyte foci promoting activity of TDNT and the primary isomers present in the technical mixture, 2,4- and 2,6-DNT. A rat hepatic initiation-promotion protocol was used in which male Fischer-344 rats were initiated with a single dose of diethylnitrosamine (DEN) (150 mg/kg, i.p.) and permitted to recover for 2 weeks. Following the recovery period, the animals were fed diets containing TDNT,2,4-DNT,2,6-DNT or phenobarbital (PB). The TDNT animals were killed after 3 or 6 weeks of feeding and the 2,4-DNT-,2,6-DNT-and PB-treated animals were killed after 6 or 12 weeks of feeding. Appropriate DEN and DNT controls were also killed at each time point. Sections from three liver lobes of each animal were stained for gamma-glutamyl transferase (GGT) and the number of GGT+ foci per cm3 (Nv) was calculated using stereological methods. TDNT feeding produced a dose-dependent increase in GGT+ foci (Nv) at 3 and 6 weeks relative to both DEN and TDNT controls. Administration of 2,4-DNT and PB produced time-dependent increases in GGT+ foci (Nv), while 2,6-DNT produced dose- and time-dependent increases. Unlike 2,4-DNT and PB, the high dose (14 mg/kg) of 2,6-dNT produced an increase in GGT+ foci in the control groups and in mean foci volume relative to the DEN control. These results establish that TDNT, 2,4-DNT and 2,6-DNT have hepatocyte foci promoting activity and that 2,6-DNT is approximately 10 times more potent than 2,4-DNT. In addition, TDNT administration neither alters hepatocyte replication following partial hepatectomy nor acts as a 'growth selection' agent in the Solt-Farber 'growth selection' model suggesting that differential effects on hepatocyte replication are not responsible for the promoting activity of TDNT. Based on previous initiation study results from our laboratory and the present data, 2,6-DNT appears to be a complete hepatocarcinogen while under the conditions of these studies 2,4-DNT is an apparent 'pure promoter'. These results provide an explanation for the conflicting DNT bioassay results.

Animals↗

PubMed1986

Quantification of axial forces in rectum-anal canal of the cat.

A newly developed probe was used to measure in vivo axial forces in the rectum-anal canal of the anesthetized cat. Spontaneous contractions of the smooth muscle of the internal anal sphincter were recorded, as were neurally evoked contractions of striated muscle of the external anal sphincter. Bilateral electrical stimulation (1-10 V, 1-5 Hz, 0.05 ms duration) of motor axons in pudendal nerves elicited two responses. One was synchronous phasic contractions of skeletal muscle fibers of the external anal sphincter that were not abolished by atropine but were by gallamine trithiodide. They occurred at short latencies (1-2 ms) and were mediated through low-threshold (1-3 V, 0.05 ms duration) efferent axons in the pudendal nerves. Contraction times ranged from 45 to 60 ms, and contraction duration ranged from 100 to 160 ms. The second response was a progressive elevation in tone of the anal canal due to contractions either of the smooth muscle of the rectum and/or that of the internal anal sphincter. The elevation in smooth muscle tone concomitant with pudendal nerve stimulation may be due to reflex activation of cholinergic neural pathways, since the response was abolished by atropine.

Anal Canal↗

PubMed1986

Streptokinase treatment of cats with experimentally induced aortic thrombosis.

An investigation was initiated to determine the dosage of streptokinase (given IV) that would consistently produce systemic fibrinolysis, as determined by laboratory evaluation, and to determine the relative safety of this drug in the cat. Results indicated that a loading dose of 90,000 IU of streptokinase (given by continuous infusion over 20 to 30 minutes) and a maintenance dosage (IV) of 45,000 IU of streptokinase/hr predictably produced systemic fibrinolysis in the cat. There were no detectable adverse affects seen on physical examination, necropsy, or histopathologic examination. Using the foregoing dosage regimen, investigation was begun to evaluate the use of streptokinase for treatment of feline thromboembolism. Aortic thrombosis was created experimentally in 15 cats. There was no clearly predictable improvement in nonspecific venous angiograms or thermal circulatory indices for the cats given streptokinase, compared with the values for the control cats. After a total of 180 minutes of treatment, the mean weight of remaining clot removed at necropsy from the aortic trifurcation was 7.3 mg in the streptokinase-treated cats, compared with 13.4 mg in the control cats.

Angiography↗

PubMed1985

Surgical treatment of punctal-canalicular fibrosis from 5-fluorouracil therapy.

5-Fluorouracil (5-FU) has been reported to cause punctal-canalicular fibrosis with resultant severe epiphora. It is reported that the epiphora will often resolve when treatment ceases or is decreased. However, this report describes a case of punctal-canalicular fibrosis so severe that bilateral conjunctivodacryocystorhinostomies were necessary. This has not been previously reported to the best of the authors' knowledge. It is recommended that ophthalmic consultation be obtained for patients in whom long-term 5-FU therapy is anticipated or who develop tearing while on therapy.

Aged↗

PubMed1985

Proposed methods for the measurement of regional renal blood flow using heat transfer analysis.

The kidney, with its heterogeneous regional perfusion in the two anatomically and functionally distinct vascular beds of the renal cortex and medulla, and with its non-uniform blood vessel geometries, presents a unique challenge for measuring intrarenal blood flow distribution. Determining whole organ perfusion, on the other hand, is comparatively simple for the kidney, but it provides relatively little information about the suspected dependency of renal excretory function on local perfusion rate. Among the variety of methods proposed for gauging regional renal blood flow, some depend on measuring one or more of the tissue's thermal properties. The most straightforward, but least reliable, involve measurements either of focal tissue temperature alone, or of regional tissue thermal gradients. Simply using heat as a diffusible indicator, however, is unreliable as a measure of blood flow, for many of the same reasons that using an inert gas in a dilution technique is unreliable. Recently developed thermal analytical methods, though, hold promise for measuring local tissue blood flow with accuracy and precision. Two of them are reviewed here. One depends on measurement of the effective thermal conductivity of a small mass of tissue by evaluating the steady state ratio between regional unidirectional heat flux across it and the associated temperature gradient in one vector along a segment of it through an imposed spheroidal heat field. The other depends on analyses of tissue temperature decay subsequent to a controlled pulse of heat delivered through a small inserted thermistor bead. Both techniques use bioheat transfer equations to deduce regional blood flow by differentiating between heat dissipation due to local thermal conductivity and that attributable to the effects of regional convection. Although both methods are unavoidably invasive, neither produces debilitating damage in the tissue volume in which perfusion is measured, nor increases local temperature or metabolism enough to affect blood flow itself. Both techniques quantify local blood flow in small volumes of tissue by detailed evaluation of the many properties of tissue and blood which affect heat transfer, and both allow for a virtually unlimited number of nearly continuous sequential measurements at short (nom. 1 min) time intervals.

Animals↗

PubMed1985

Potentiation of lung vascular response to endotoxin by superoxide dismutase.

We studied the effects of superoxide dismutase (SOD), an enzyme that converts superoxide into peroxide, on the cardiopulmonary response to endotoxin in sheep. Sheep (n = 18) were prepared for chronic measurement of cardiopulmonary variables, including lung lymph flow, by surgically implanting catheters under halothane anesthesia. Nine of the animals were studied before and after the administration of endotoxin (0.75 microgram/kg) with and without SOD. An additional nine animals received SOD without the lipopolysaccharide. Endotoxin produced an increase in lung lymph flow that was initially associated with a marked pulmonary arterial (PA) hypertension and reduced lymph-to-plasma protein ratio (L/P). The lymph flow remained elevated later in the response, but there was only a mild increase in PA pressure, and the L/P was normal. There was also a fall in blood neutrophils and in cardiac index. SOD increased this secondary elevation in lung lymph flow, and the corresponding L/P was greater than the preendotoxin value. The fall in neutrophil count, cardiac output, and the elevation in PA pressure seen with endotoxin were not affected by SOD. When administered in the absence of endotoxin, SOD produced no perceptible change in the cardiopulmonary and lymph values. We conclude that peroxide, hydroxyl ion, and/or other free radicals formed by the action of SOD must be responsible for a portion of the endotoxin response rather than superoxide itself.

Animals↗

PubMed1984

Effect of inhibitors of the lipoxygenase pathway on mouse myoblast fusion.

In this study we examined the effects of inhibitors of the lipoxygenase and cyclooxygenase pathways on mouse myoblast fusion. The fusion of cloned mouse myoblasts was markedly inhibited, in a dose-dependent manner, when cells were cultured in medium supplemented with either phenidone (1-phenyl-3-pyrazolidione) or BW755c (3-amino-1-(3-tri-fluoromethylphenyl)-2-pyrazoline), drugs which have been reported to inhibit lipoxygenase and cyclo-oxygenase activities. Fusion was also inhibited when these cells were cultured in medium supplemented with esculetin (6,7-dihydroxycoumarin) which has been reported to inhibit lipoxygenase activity. Removal of the above inhibitors resulted in a return to control levels of fusion. Fusion was not demonstrably inhibited with aspirin (acetylsalicylic acid) and only inhibited to a minor extent with indomethacin (1-(p-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetic acid); both of these drugs are inhibitors of cyclo-exygenase activity.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

PubMed1984

Ibuprofen and diphenhydramine reduce the lung lesion of endotoxemia in sheep.

Endotoxin (0.75 micrograms/kg) was administered to unanesthetized sheep with and without premedication with ibuprofen, a cyclooxygenase inhibitor, and diphenhydramine, an antihistamine. The effect of the endotoxin on cardiopulmonary and lung lymph data and their alteration by the drug regimen was assessed. The cardiopulmonary responses to endotoxin can be defined into two phases. In phase I there is an elevation in protein-poor lung lymph flow, in pulmonary artery pressure (PA), and in hematocrit, and a reduction in cardiac index and leukocyte count. Phase II occurs late and shows much the same changes as phase I except that the PA is not as high and the lymph protein is increased. The drug combination (ibuprofen and diphenhydramine) virtually eliminates the phase I response. The phase II changes in lymph flow and protein content are affected by diphenhydramine but not ibuprofen. The cardiovascular changes which occur during this period are not affected by either agent.

Animals↗

PubMed1984

First year of life after the use of atenolol in pregnancy associated hypertension.

We describe the results of a prospective study in which 120 women who developed hypertension in the last trimester of pregnancy were randomly allocated in double blind manner to atenolol or placebo. The mean duration of treatment was five weeks. The only difference between groups during the neonatal period was in respiratory distress syndrome, mainly related to spontaneous premature labour, which occurred in six placebo group babies but in none from the atenolol group. Fifty five children from each group have been followed to 1 year of age. All in the atenolol group are developing normally but one child from the placebo group is brain damaged. These findings do not suggest any short or medium term paediatric complications after the use of beta blockers in pregnancy.

Atenolol↗

PubMed1984

Inhalation injury and positive pressure ventilation in a sheep model.

The mortality rate of inhalation injury was lowered in six chronically instrumented sheep through positive pressure ventilation and positive end-expiratory pressure (PEEP). Six range ewes were prepared for study by implanting catheters to measure lung lymph flow and cardiopulmonary variables. After surgery, these animals were studied in the unanesthetized state and then subjected to an inhalation by insufflating them with smoke from burning cotton. Following the smoking procedure, the animals were studied for 72 hr. All had marked falls in arterial oxygen tension and they developed dyspnea within 24 hr. The inhalation injury produced a marked change in lung lymph flow concomitant with an elevation in the lymph to plasma (L/P) oncotic pressure ratio. This is characteristic of a change in microvascular permeability to protein. A tracheostomy was performed at 72 hr and the animals were connected to positive pressure ventilators with PEEP. All six animals survived. It was concluded that the sheep lung lymph preparation is a very suitable model for the study of inhalation injury and positive pressure ventilation.

Animals↗

PubMed1984

Failure of a protease inhibitor to affect the cardiopulmonary response to endotoxin when combined with a cyclooxygenase inhibitor.

The administration of endotoxin produces an early increase in hydrostatic pressure and pulmonary lymph flow, which is associated with elevated levels of thromboxane A2 in the lymph and can be blocked by the cyclooxygenase inhibitor ibuprofen. Two hours after the administration of endotoxin a secondary response is seen. The pulmonary lymph flow is elevated in association with a change in microvascular permeability to protein, this phase of the response can be reduced by the administration of the proteolytic enzyme inhibitor gabexate mesilate. In the present study we administered both compounds to eight sheep prepared for chronic cardiopulmonary and lung lymph studies to reduce both phases with the drug combination. The phase I response was reduced but the changes in lung lymph flow, associated with the phase II response, were unaffected by treatment. It is concluded that the effect of gabexate mesilate on the secondary response to endotoxin must in some way be related to the release of prostanoids.

Animals↗

PubMed1983

An improved method for water vapor detection.

We describe improvements in and details for the construction, calibration and use of a device using a thermal conductivity cell for the measurement of low-level rates of water evaporation (E) from a small surface area. E is measured from 0.0 to 1.0 mg . min-1 with a correlation coefficient of 0.999 between measured and independently verified rates and amounts of water evaporation. Data are available as a recordable analog d.c. voltage as well as in digital display for E and for the amount of water evaporated during an operator defined time period. The device we describe is noninvasive and it is designed to be constructed of conventional components. It is useful not only for measuring transcutaneous water diffusion in normal and diseased skin, but also it is adequately sensitive and rapidly responding to follow thermoregulatory and psychogenic sweating in small (nom. 1.0 cm2) skin areas. It can also be used to measure accurately and precisely the rates at which water is adsorbed by and removed from inanimate materials, as well as to determine how much water they store.

Animals↗

PubMed1983

Temperature regulation in adult quail (Colinus virginianus) during acute thermal stress.

1. Evaporative heat loss, O2 consumption, CO2 production, and internal body temperature were measured in unanesthetized, unrestrained bobwhite (Colinus virginianus) at specific ambient temperatures (Ta). 2. No significant change in body temperature occurred at any Ta tested, but metabolic heat production (H) increased from 42.17 W/m2 at Ta 35 degrees C to 102.89 W/m2 at Ta 10 degrees C. 3. Evaporative heat loss (E) increased approximately two-fold from Ta 10-35 degrees C, with E/H increasing exponentially over the same temperature range. 4. No significant change in thermal insulation occurred from Ta 10-30 degrees C. 5. Combined convective and radiative heat transfer for the bobwhite was 2.96 W/m2 X C from Ta 10-35 degrees C.

Animals↗

PubMed1983

Action of an opiate receptor blocker on ovine cardiopulmonary responses to endotoxin.

The involvement of endorphins in the ovine cardiopulmonary response to endotoxin was evaluated by measuring blood levels of opiate receptor binding substances and administering the opiate receptor blocking agent naloxone prior to and after the administration of lipopolysaccharide. The animals were prepared for chronic study by placement of cardiovascular catheters and cannulation of the lung lymphatic at least 1 wk prior to study. The sheep were given endotoxin (0.75 micrograms/kg) and studied for 6 h. This was accomplished twice in the same animal. Naloxone (2 mg/kg bolus + 2 mg X kg-1 X h-1) was given with one of the two doses of the lipopolysaccharide. The response to endotoxin could be divided into two phases. In phase 1, there was an increase in protein-poor lung lymph and a marked increase in pulmonary artery pressure. In phase 2, the pulmonary lymph flow was elevated but the lymph protein level was higher than in phase 1. The pulmonary artery pressure, however, was near normal. During both phases leukocytes and cardiac output were reduced and the hematocrit was elevated. There was an increase in opiatelike materials in the plasma of these animals, and the response to endotoxin was partially blocked by naloxone. This suggested that endorphin-like materials were involved in the response to endotoxin.

Animals↗

PubMed1983

Effect of hypercapnia and cerebral perfusion pressure on cerebrospinal fluid production in cat.

Brain ventricles of anesthetized cats were perfused with an artificial cerebrospinal fluid (CSF) containing inulin (or [14C]dextran) and 3H-labeled sucrose while each animal respired in turn either room air or an 8-11% CO2-in-air gas mixture. Perfusion inflow (Vi) and outflow (Vo) rates and concentrations of the test molecules were measured to calculate steady-state CSF production (Vf), CSF absorption (Va), and ependymal sucrose permeability (Ksuc). During respiratory acidosis Vf varied inversely as a function of normocapnic Vf, Ksuc increased, and Va was the same as during normocapnia. Vf increased with cerebral perfusion pressure (CPP) during normocapnia but was inversely related to it during hypercapnia. When a normocapnic animal's CPP is high in the range 70-105 Torr, its Vf will also be high, but it will increase its Vf little or not at all during hypercapnia. In the same range, if its CPP is low, its Vf will also be low, but its Vf will increase predictably fourfold or more when it breathes CO2. CPP is an influential determinant of Vf at any level of acid-base balance, possibly due to variations in blood flow at CSF production sites.

Acidosis, Respiratory↗

PubMed1983

Cerebrospinal fluid transients induced by hypercapnia.

Ventriculocisternal perfusion studies using tracers have shown that hypercapnia causes a transient increase in cerebrospinal fluid (CSF) outflow rate (displaced CSF volume, Vd) and a decrease in CSF effluent tracer concentration (tracer-free CSF, CSFtf). This dilution could be due to an increase in CSF formation rate (Vf) and/or to displacement of unequilibrated CSFtf sequestered in poorly mixed compartments. To facilitate convection in the subarachnoid spaces, we used a "stop-flow" procedure (by clamping the cisternal outflow tube while infusion was constant) in anesthetized cats during ventriculocisternal perfusion with mock CSF containing [14C]dextran. Each animal spontaneously breathed air, then 5% CO2 both before and after stopflow. Although Vd and the times over which Vd and CSFtf were defined were unaffected, CSFtf was decreased by 50% after stop-flow. We conclude that during ventriculocisternal perfusion, mixing is incomplete in CSF spaces, and that unequilibrated CSF contributes significantly to the reduced tracer concentration in Vd during acute hypercapnia. To determine whether Vf transiently increases in response to CO2 breathing, or to any perturbation causing craniospinal fluid redistribution, homogeneity in CSF spaces must be verified.

Animals↗

PubMed1983

Reproducibility of cardiopulmonary effects of different endotoxins in the same sheep.

This study compares qualitative and quantitative differences between the cardiopulmonary responses to Salmonella typhimurium and Escherichia coli 055:B5 endotoxins (Difco) in the same sheep model. Lipopolysaccharides, 0.75 micrograms/kg, were infused into chronically instrumented sheep over 30 min. Cardiopulmonary and pulmonary lymph flux data were collected for 2 h prior to and 6 h following this. One week later the sequence was repeated with another endotoxin. The administration of the two endotoxins was varied: some received S. typhimurium first; others received E. coli. A total of 13 animals were studied; 8 had intact pulmonary lymphatic catheters. Following each injection of endotoxin these animals showed a typical response of early high pressure-mediated increase in pulmonary lymph flow and later lymph flow elevation associated with a very mild increase in microvascular pressure and lymph with normal protein levels. These changes were associated with hemoconcentration, lowered arterial oxygen partial pressure, cardiac index, and blood neutrophil count. It is concluded that Difco S. typhimurium and E. coli endotoxins are similar in their mechanism of action and potency and can be studied in the same animal.

Animals↗

PubMed1983

Role of lymphocytes in the ovine response to endotoxin.

The involvement of thymocytes in the cardiopulmonary response to endotoxin was studied in chronically instrumented sheep. Four hours after the administration of 0.75 microgram/kg of endotoxin the blood levels of thymocytes were less than 25% of the control value, at a time when there was a marked fall in the cardiac index and a rise in pulmonary lymph flow. In a second series of experiments sheep were depleted of their thymocytes by the administration of antithymocyte serum. When endotoxin was given to these animals the cardiac output did not fall to the same extent, nor did the hematocrit rise as much as it did in the intact animal. It thus appears that the thymocyte may play a contributing role in the cardiopulmonary response to endotoxin.

Animals↗