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Biomedical subjects

R G Carroll

Publications and source records attributed to R G Carroll.

At least 55 records · Page 3Linked to original sources
PubMed1993

Implications of adult education theories for medical school faculty development programmes.

Adult education principles have impacted the approach used by many faculty development programmes. Underlying themes of immediacy of application, task centered opportunities to practice skills, and feedback on efforts are common to most popular approaches. Less common are instances where the need to know is initially communicated, or provision of opportunities to direct course content. Incorporation of sound adult educational principles into the design of faculty development programmes should enhance its reception by the faculty, and increase its value to the school.

Education, Continuing↗
PubMed1992

Signal transduction through crosslinking CD7 and IgM-Fc receptors that inhibits T-cell proliferation.

We have previously suggested a possible involvement of CD7 and/or the putative receptor for IgM-Fc (FcRmu) in the downregulation of T-cell responses to mitogen and alloantigen. In this report, we examined the effect of ligand-receptor interaction upon T-cell proliferation by using anti-CD7 monoclonal antibodies (mAbs) and purified human IgM (HIgM) and showed that crosslinking CD7 and/or FcRmu on T cells resulted in significant inhibition of mitogen- and alloantigen-induced proliferative responses. In most cases, crosslinking of FcRmu alone or together with CD7 receptors on peripheral blood lymphocytes (PBLs) resulted in more potent suppression of T-cell proliferation than that caused by crosslinking CD7 alone. Examination of potential inhibitory mechanisms revealed that crosslinking CD7 and FcRmu does not reduce cell viability or the expression of T-cell markers that are important for T-cell activation or proliferation. However, crosslinking CD7 and/or FcRmu of PBLs significantly reduced phytohemagglutinin (PHA)-induced IL-2 production and rendered PBLs unable to utilize exogenously added human recombinant IL-2 (rIL-2). Further examination of possible signal transduction that might be associated with crosslinking CD7 and/or FcRmu receptors indicated a marked reduction in the magnitude and duration of intracellular calcium (Ca++)i released in response to PHA. These findings suggest that crosslinking CD7 and FcRmu inhibits T-cell activation and proliferation by a calcium-dependent mechanism that inhibits IL-2 production and/or utilization.

Antigens, CD↗
PubMed1992

Functional studies of left upper quadrant mass aid management of idiopathic thrombocytopenic purpura.

ITP (idiopathic thrombocytopenic purpura) causes rapid sequestration and destruction of thrombocytes by the spleen, liver, bone marrow, and reticuloendothelial elements of other organs. The usefulness of multiple radionuclide functional imaging procedures in the management of a 34-year-old woman with chronic ITP, two splenectomies (removal of the initial spleen and then a hypertrophied accessory spleen), and the failure of chemotherapy to control her thrombocytopenia, are discussed. A combination of In-111 oxine autologous platelet imaging, liver/spleen imaging, disofenin (liver/gallbladder) imaging, and glucoheptonate renal imaging demonstrated that her platelets were being sequestered by a markedly enlarged left hepatic lobe extending to the left lateral wall, with a small amount in the kidneys and lungs, and that there was no second accessory spleen.

Adult↗
PubMed1992

Role of the sympathetic nervous system in the alcohol-guanabenz hemodynamic interaction.

The present study evaluated the contribution of the sympathetic nervous system to the adverse hemodynamic action of ethanol on hypotensive responses in conscious unrestrained spontaneously hypertensive rats. Ethanol caused a dose-related attenuation of the hypotensive effect of guanabenz. An equivalent hypotensive response to sodium nitroprusside was not influenced by ethanol, which indicates a potential specific interaction between ethanol and guanabenz. Alternatively, it is possible that a preexisting high sympathetic nervous system activity, which occurred during nitroprusside infusion, may mask a sympathoexcitatory action of ethanol. Further, ethanol (1 g/kg) failed to reverse the hypotensive effect of the ganglionic blocker hexamethonium. This suggests that a centrally mediated sympathoexcitatory action of ethanol is involved, at least partly, in the reversal of hypotension. In addition, the antagonistic interaction between ethanol and guanabenz seems to take place within the central nervous system and involves opposite effects on central sympathetic tone. Finally, changes in plasma catecholamines provide supportive evidence for the involvement of the sympathetic nervous system in this interaction. In a separate group of conscious spontaneously hypertensive rats, ethanol (1 g/kg) reversed the guanabenz-evoked decreases in blood pressure and plasma catecholamine levels. It is concluded that (i) ethanol adversely interacts with centrally acting antihypertensive drugs through a mechanism that involves a directionally opposite effect on sympathetic activity, and (ii) a sympathetically mediated pressor effect of ethanol is enhanced in the presence of an inhibited central sympathetic tone.

Animals↗
PubMed1992

Increase in renal magnesium overflow following aortotomy-induced hemorrhage in pigs.

Hemorrhage causes an increase in plasma Mg++ levels. This article identifies some of the tissues contributing to the hemorrhage induced increase in plasma Mg++. Anesthetized, splenectomized pigs were subjected to a 5 mm aortotomy. Blood samples from the abdominal aorta, inferior vena cava, pulmonary artery, hepatic portal vein, and renal vein were sampled for Mg++ changes caused by this uncontrolled hemorrhage. Aortotomy produced a rapid drop in arterial pressure and cardiac output, both of which remained depressed for the following 120 minutes (P less than 0.05). By 120 minutes, 6 of the 8 pigs survived, but three of the six survivors showed signs of cardiovascular decompensation. A significant increase in arterial plasma Mg++ was indicated by a paired t-test (P less than 0.05). Analysis of the venous samples also revealed a significant increase during the post-aortotomy period. Renal venous and hepatic portal venous plasmas both showed increases greater than that in the arterial plasma. The renal and splanchnic tissues, then, were partly responsible for the increase in the arterial Mg++ which follows hemorrhage.

Animals↗
PubMed1992

Pharmacokinetics of indium-111-labeled B72.3 monoclonal antibody in colorectal cancer patients.

Mean time parameters provide a new approach to plasma pharmacokinetics of radiolabeled Mabs that may show important patient differences affecting diagnosis or treatment. We determined mean time pharmacokinetic parameters for 11 patients entered in a Phase I/II clinical trial for detection of colorectal cancer. Patients were administered 0.5-2 mg of B72.3 anti-TAG-72 radiolabeled with 3.5-5 mCi of 111In, plasma activity was measured over time. Mean time pharmacokinetic parameters were (mean +/- s.e.m.): mean residence time; body (MRTB) 88.9 +/- 7.2 hr, central (MRTC) 73.8 +/- 6.0 hr; mean transit time, central (MTTC) 41.1 +/- 9.0 hr; mean residence time, periphery (MRTP) 15.1 +/- 3.4 hr; intrinsic mean residence time, periphery (IMPTP) 39.0 +/- 7.6 hr; mean transit time, periphery (MTTP) 24.0 +/- 6.7 hr; probability of distribution (PRD) 50% +/- 10%; and n compartmental cycles of 4.54 +/- 2.3 times. In patients with increased circulating specific TAG-72 antigen, MRTC greater than MTTC and n much greater than 1. In patients without specific antigen, MRTC approximately equal to MTTC and n much less than 1. Pharmacokinetic studies may identify patients who do not have the tumor produced target antigen for the specific Mab and may provide an opportunity to select another specific Mab with an increased chance for successful diagnosis or treatment.

Aged↗
PubMed1991

Intraoperative gamma detection probe with presurgical antibody imaging in colon cancer.

In this study, presurgical gamma camera imaging and an intraoperative gamma detection probe were used in 12 consecutive patients 6 to 22 days after infusion with indium 111-labeled anticarcinoembryonic antigen monoclonal antibody (111In-MoAb). In three of 11 patients who underwent laparotomy, clinical management was affected by the probe findings: localization of occult retroperitoneal disease, identification of an occult cecal lesion, and localization of residual disease at a site of local recurrence. Of all intra-abdominal lesions seen using any method, the probe identified 18 (86%) of 21, compared with 14 (67%) of 21 with the 111In-MoAb scan, 10 (48%) of 21 by computed tomographic scan, and 16 (76%) of 21 after surgical exploration. Uptake of 111In-MoAb in the portal (n = 3) and mediastinal (n = 3) lymph nodes was not associated with histologic findings of malignant neoplasms. For all pathologically confirmed extrahepatic and nonportal sites of cancer, the probe localized nine of nine, compared with five of nine by 111In-MoAb scan, two of nine by computed tomographic scan, and six of nine by surgical exploration. Important clinical uses of the intraoperative probe included occult lesion identification, localization of areas with 111In uptake shown with MoAb scanning, and verification of complete resection of areas with 111In-MoAb uptake.

Abdominal Neoplasms↗
PubMed1990

Human biodistribution of 111In-labeled B72.3 monoclonal antibody.

The murine IgG1 monoclonal antibody B72.3 reacts with human colorectal, breast, lung, pancreatic, gastric, and ovarian tumors. Human biodistribution studies using intact 131I-B72.3 have been reported by Carrasquillo et al. (J. Nucl. Med., 29: 1022-1030, 1988). We have performed similar studies on five patients using i.v. infusion of 20 mg of intact 111In-B72.3 (Cytogen Corp.). Serum clearance is similar with a t1/2 of 64.2 h (range, 44-80) for 111In-B72.3 and 65 h (range, 32-106) for 131I-B72.3 (J. A. Carrasquillo et al., J. Nucl. Med., 29: 1022-1030, 1988). However, organ biodistribution is markedly different. For 131I-B72.3, hepatic and splenic clearance mirrors blood pool clearance (J. A. Carrasquillo et al., J. Nucl, Med., 29: 1022-1030, 1988). For 111In-B72.3, there is rapid uptake in tumor, liver, spleen, kidney, lumbar spine, and testes by 2-6 h with no significant clearance over the next 9 days. For 111In-B72.3, quantitative analysis of liver (from biopsy specimens), spleen, kidney, and lumbar spine (from scintiphoto regions of interest after background subtraction and attenuation correction) shows the following peak organ biodistributions in percentage infused dose: liver, 32%; spleen, 3.9%; kidneys, 3.5%; and lumbar vertebral bodies (marrow sample), 2.7%. For both 111In-B72.3 and 131I-B72.3, the principal route of excretion from the body is urinary with excretion rate of 131I faster than 111In. The marked differences between 111In-B72.3 and 131I-B72.3 biodistribution and clearance strongly influence the dosimetry, immunodetection, and immunotherapeutic potentials of B72.3 MoAb.

Aged↗
PubMed1990

Serum magnesium increases following severe hemorrhage in dogs blocked by verapamil treatment.

The opening of voltage sensitive calcium channels is an important event in the progression of irreversible shock, allowing the entry of toxic amounts of calcium (Ca2+) into the cells. Because intracellular magnesium (Mg2+) can efflux through these same channels, changes in serum Mg2+ may reflect the patency of these channels. In this study, electrolytes and selected serum enzymes were monitored in chronically instrumented conscious dogs to follow the progression of shock following a fixed volume hemorrhage. Plasma enzymes indicative of liver damage were elevated only in the terminal phase of hemorrhagic decompensation. A significant increase in serum Mg2+ was evident 60 min following hemorrhage, even though arterial pressure was still recovering. Serum Mg2+ continued to rise throughout the recovery and decompensating phases of shock. Verapamil treatment, which increased survival time and survival rate, significantly attenuated the changes in serum Mg2+ which normally followed hemorrhage. These results indicate that serum Mg2+ may be a useful indicator of the severity and the progression of hemorrhagic shock.

Alkaline Phosphatase↗
PubMed1990

Renal vascular response to amino acids: effect of pancreatectomy.

We ascertained the importance of glucagon in modulating the renal hemodynamic response to amino acid (AA) infusion in anesthetized dogs. In controls (n = 6), AAs (L-serine, alanine, and proline; 0.051 mmol.kg-1.min-1 iv) elevated renal blood flow (RBF) and glomerular filtration rate (GFR) by 35 and 34%, respectively, while elevating arterial plasma glucagon-like immunoreactivity (AGLI) by 96 pmol/l. In control pancreatectomized (PX) dogs (n = 6), all parameters remained at control values over 2 h. In PX dogs, AAs (n = 6) failed to reproduce the renal hemodynamic and AGLI responses elicited by AAs in controls. In PX dogs infused with AAs, replacement of AGLI (n = 6) to an incremental plasma level of 111 pmol/l, a level no different than that produced by AAs in controls, elevated RBF and GFR by 25 and 26.5%, respectively. These hemodynamic responses were 71 and 78%, respectively, of the total responses elicited by AAs in controls. In PX dogs infused with glucagon alone (0.86 pmol.kg-1.min-1; n = 6), an incremental change in AGLI of 112 pmol/l was accompanied by only small increases in RBF and GFR (9%). These data suggest the importance of glucagon in modulating the renal hyperemia and hyperfiltration ascribed to AA infusion in anesthetized dogs.

Amino Acids↗
PubMed1989

Transcutaneous oxygen tension measurements during hemorrhagic hypoperfusion using Trendelenburg and the pneumatic antishock garment.

Transcutaneous oxygen tension (PtCO2) was observed during hemorrhagic hypoperfusion using four therapeutic modalities: pneumatic antishock garment (PASG), 20 degrees Trendelenburg positioning, combined PASG-Trendelenburg, and whole blood infusion. Anesthetized mongrel dogs were mechanically ventilated. A heated transcutaneous oxygen sensor was applied to the skin overlying the sternum. Animals were bled over 10 min of 25% of their calculated blood volume. A therapeutic intervention was applied at the onset of hemorrhage (PASG, Trendelenburg, PASG-Trendelenburg or control). All animals were observed for 20 min, then during a 10-min shed blood reinfusion period, and for 20 min thereafter. PtCO2 was measured continuously and the following were measured serially: cardiac output, mean arterial pressure (MAP), mixed venous oxygen tension (MvO2), and arterial oxygen tension (PaO2). Cardiac index (CI) and the oxygen extraction ratio were calculated. PtCO2 decreased immediately after hemorrhage in all animals. Control values remained consistently below values for active interventions during this time. All groups regained baseline levels of PtCO2 after reinfusion of shed blood volume. PaO2 remained nearly constant during all experiments. MAP and CI fell in all groups following hemorrhage but did so less precipitously in the PASG group. The PASG and PASG-Trendelenburg groups showed the greatest increase in CI during reinfusion. These results suggest that when PtCO2 is relied upon as an indicator of adequacy of resuscitation during moderate hemorrhagic shock, that cutaneous perfusion may be improved by the PASG or Trendelenburg position, and that perfusion is most effectively restored by blood infusion.

Animals↗
PubMed1989

Verapamil treatment of canine hemorrhagic shock.

The entry of calcium (Ca++) into ischemic cells is the first of a series of steps leading to irreversible cellular damage. This study examined the ability of verapamil, which may delay or diminish the injury-induced influx of Ca++, to prolong survival in three groups of chronically instrumented dogs subjected to a single, rapid hemorrhage. In untreated animals (group 1, N = 6), hemorrhage decreased mean arterial blood pressure from 101 +/- 3 mm Hg to 23 +/- 2 mm Hg. Following hemorrhage, arterial pressure recovered to 61 +/- 5 mm Hg before the secondary fall (decompensation) occurred. As decompensation progressed, arterial pressure fell to 25 mm Hg, and the animals were euthanized. In group 2 (N = 6), verapamil treatment (2 mg bolus, 1 mg/hr infusion) was initiated 30 minutes before the hemorrhage. This treatment significantly increased both the time to decompensation (184 +/- 15 minutes vs 72 +/- 9 minutes) and survival time (262 +/- 20 minutes vs 128 +/- 8 minutes). Arterial pressure recovery during the first 60 minutes following hemorrhage, however, was not affected by the verapamil pretreatment. Verapamil treatment immediately after the hemorrhage (group 3, N = 4) increased the survival rate to 75% (three of four animals). These results indicate that calcium channel blockade may be a useful initial intervention in the treatment of hemorrhagic shock.

Animals↗
PubMed1989

Electricity and the body: a precollege demonstration laboratory.

The active recruitment of students to scientific careers is essential to the continued health of the basic medical sciences. One step in this process involves an early exposure to the practice and possibilities of scientific investigation. Physiology faculty of colleges and professional schools are uniquely poised to demonstrate the importance of science to younger students. This report describes a laboratory demonstration that is designed for groups of middle-school and high-school students as a part of a medical school tour. With appropriate modifications, a similar approach can be used to demonstrate the principles of scientific investigation to students at any level. Subsequent discussions can be used to illustrate the potential benefits of medical research. Presentations such as the one contained in this paper may aid in the recruitment of future physiologists and physicians.

Electrocardiography↗
PubMed1989

Sustained increases in plasma epinephrine concentration do not modulate renin release.

We examined the relationship between plasma renin activity (PRA) and renal arterial pressure (RAP) during 1) control conditions, 2) acute, and 3) chronic intravenous epinephrine (EPI) infusion (125 ng.kg-1.min-1). In eight conscious uninephrectomized dogs maintained on a normal sodium intake, the renin stimulus-response curve (RSRC) was determined by a stepwise reduction in RAP with an inflatable occluder around the renal artery controlled by a servo unit. The RSRC could be approximated by two lines intersecting at a threshold pressure (approximately 20 mmHg below control RAP). In the high-pressure range, PRA was relatively insensitive to changes in RAP, whereas, below threshold pressure, changes in RAP had large effects on PRA. During acute EPI infusion there was approximately a 40% increase in heart rate (control = 57 +/- 3 beats/min) and hematocrit (control = 30 +/- 1%) in association with a rise in plasma EPI concentration from 73 +/- 16 to 1,413 +/- 100 pg/ml; mean arterial pressure (MAP) was unchanged (94 +/- 3 mmHg). Moreover, EPI acutely increased basal PRA from 0.3 +/- 0.1 to 0.8 +/- 0.3 ng angiotensin I.ml-1.h-1 and shifted the RSRC to the right (increasing threshold pressure 7 mmHg) without altering the slope of the RSRC curve either above or below threshold pressure. In contrast, although plasma EPI concentration and hematocrit remained elevated during chronic EPI infusion, heart rate and basal PRA returned to preinfusion values. In addition, there were no significant long-term changes in MAP or in any of the parameters of the RSRC.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Transient increase in plasma catecholamines following hypertonic/hyperosmotic fluid administration in conscious rats.

Plasma norepinephrine and epinephrine levels were monitored to determine possible alterations of the sympathetic nervous system caused by hypertonic fluid administration. Iv infusion (3.5 ml/kg, 1 min) of 7.5% NaCl/6% Hespan transiently increased both plasma norepinephrine and epinephrine levels to 197 +/- 28% and 220 +/- 30% of control, respectively, at 1 min. These increases were no longer significant 5 or 15 min following infusion. A brief hypotension was also observed immediately following hypertonic fluid administration. Thus, prolonged sympathetic activation does not occur following hypertonic fluid infusion in normovolemic conscious rats.

Animals↗
PubMed1988

Single hemorrhage: a clinically relevant canine model of hemorrhagic shock.

Clinically encountered hemorrhagic shock is usually caused by a single, rapid hemorrhage secondary to trauma. Experimental models of shock, however, have utilized anesthetic agents and hemorrhage protocols which may compromise the clinical relevance of their findings. This report characterizes the response of conscious, splenectomized dogs to a single hemorrhage of varying rates and volumes, uncomplicated by the presence of anesthetic agents. The duration of a 40 ml kg-1 hemorrhage affected the magnitude of blood pressure recovery, but did not alter the decompensating drop in blood pressure. The shortest hemorrhage duration was chosen for further study, as the blood pressure profile for this hemorrhage duration demonstrated most clearly the recovery, plateau, and decompensation phases. Increasing the hemorrhage volume to 43 ml kg-1 caused a reproducible decrease in the magnitude of the blood pressure recovery, the time to decompensation, and the time to death. Splenectomized dogs, then, demonstrate a reproducible response to a fixed-volume hemorrhage, making chronically instrumented conscious dogs a good animal model with which to study the progression of hypovolemic shock.

Animals↗