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Biomedical subjects

J M Morgan

Publications and source records attributed to J M Morgan.

At least 91 records · Page 5Linked to original sources
PubMed1994

Inhibition of angiotensin-converting enzyme with libenzapril in normotensive males.

The effect of intravenous (i.v.) libenzapril was studied in six healthy males by administering i.v. angiotensin I (AI) administered in stepwise increments of 20 ng/kg/5 min until the subjects' systolic blood pressure (SBP) had increased 20-30 mm Hg above baseline. The mean baseline infusion of 63 ng/kg/5 min resulted in a significant (P < 0.05) increase in the ratio of AII to AI plasma levels from 0.52 +/- 0.46 to 7.92 +/- 4.48 and a SBP increase of 120 +/- 7.1 to 147 +/- 5.6. Within 15 minutes of starting the 1-mg infusion of libenzapril over 1.5 hours, the AII/AI ratio decreased to baseline values, and the SBP had returned to baseline in 1 hour. Repeat AI challenges at 3.5 and 5 hours postdose did not increase SBP significantly. Even the 6.5-hour challenge demonstrated only a slight increase in SBP, with an AII/AI ratio of 0.26. At 24 hours, SBP was only 40% of the baseline response, demonstrating that libenzapril is a potent long-acting ACE inhibitor.

Adult↗
PubMed1994

Possible role of tissue-bound calcium ions in citrate-mediated high-temperature antigen retrieval.

High-temperature preheating of sections in the presence of a salt (e.g., citrate) or a protein denaturant (e.g., urea) solution has been shown recently to provide a reliable alternative to tissue proteolysis for antigen retrieval from formaldehyde-fixed, paraffin-embedded tissues. However, the underlying mechanism of action of this form of pretreatment remains highly speculative. In this study, we show that calcium chelating agents such EDTA and EGTA are more effective than citrate in the retrieval of a citrate-sensitive nuclear antigen, Ki-67. Also, sodium carbonate and another calcium precipitating agent are both able to effect antigen retrieval at high temperatures. The overall data therefore suggest that either the chelation or the precipitation of tissue-bound calcium ions, and perhaps also other divalent metal cations, is a critical step in salt-mediated antigen retrieval. As a corollary, it is suggested that tight complexing of calcium ions or other divalent metal cations with proteins during formaldehyde tissue fixation is responsible for the masking of certain antigens.

Antigens↗
PubMed1994

[Moist autoclaving. A simplified method for antigen unmasking].

Wet autoclaving is a simple, reliable and time-effective method for antigen retrieval in routinely processed archival material. Both routine diagnostic (e.g., oestrogen and progesterone receptors, cytoskeletal proteins) and research antibodies (e.g. various p53 antibodies, mdm-2, bcl-2, MIB-1) are reported to demonstrate its application. We autoclaving may allow successful application of antibodies in paraffin-embedded tissues designed for use on frozen sections. The technique has the potential to reliably handle up to 200 sections at a time, without evidence of any significant damage to the sections or nuclear morphology.

Antigens, Neoplasm↗
PubMed1994

In vitro analysis of shed blood from patients undergoing total knee replacement surgery.

One method used to obtain autologous blood includes collection of wound drainage postoperatively. The decision to wash wound drainage before infusion is left to individual institutions. The composition of blood collected from joint spaces has not been adequately evaluated. Wound drainage from total knee replacement was collected into a cardiotomy reservoir, without anticoagulation, for 4 hours after surgery. Coagulation parameters were evaluated on the washed supernatant and unwashed supernatant. The most significant findings were the following: 1. Modified prothrombin time: washed supernatant and unwashed supernatant were substituted for tissue thromboplastin reagent. The unwashed supernatant initiated fibrin formation (mean, 108 seconds), whereas the washed supernatant did not (mean, > 150 seconds, P = .01). 2. Euglobulin lysis times: Mixtures containing 50% normal plasma and 50% washed supernatant or unwashed supernatant were used to determine plasmin activation (unwashed supernatant + normal plasma = 24 minutes; washed supernatant + normal plasma = 106 minutes; P = .03). Lower euglobulin lysis times indicates increased plasmin activity. 3. Fibrin degradation products: Concentrations were significantly elevated in unwashed supernatant (mean 10,240 micrograms/mL) versus washed supernatant (mean 5 micrograms/mL, P = .02). Fibrin degradation products are inhibitors of fibrin formation and platelets. The authors conclude the unwashed supernatant from wound drainage collected after total knee replacement contains activated components of the soluble coagulation and fibrinolytic systems, and these substances can be significantly reduced with washing.

Blood Coagulation Tests↗
PubMed1994

Predicting Ixodes scapularis abundance on white-tailed deer using geographic information systems.

We collected 1,410 Ixodes scapularis from 139 white-tailed deer in Kent County, Maryland during the 1990 hunting season. A geographic information system was used to extract 41 environmental variables in the areas surrounding the collection sites of the deer. Stepwise linear regression was used to evaluate the association between the abundance of ticks on deer and the environmental data. A significant statistical association was observed between the abundance of I. scapularis and seven environmental variables (R = 0.69). Tick abundance was negatively correlated with urban land use patterns, wetlands, the amount of privately owned land, soils that tended to be saturated with water, and one drainage system. Tick abundance was positively correlated with well-drained, sandy soils having low water tables. These results indicate that geographically referenced environmental data may be useful in anticipating the risk of exposure to vectors over large areas.

Animals↗
PubMed1994

Pharmacodynamics of a continuous intravenous infusion of CGP-35126 recombinant human insulin-like growth factor-I (rhIGF-I) on glucose and insulin levels in healthy males.

Recombinant human insulin-like growth factor-I (rhIGF-I) was evaluated in 7 healthy males to determine the pharmacodynamics on glucose and insulin levels. Each subject received an initial intravenous infusion of normal saline and on the following day, rhIGF-I at a rate of 21.4 micrograms/kg/h over 7 hours. The subjects' fasting baseline glucose and insulin levels were not statistically different (p > 0.05) from their pre-dose levels. Compared to the saline (control) infusion, glucose levels were statistically lower (p < 0.05) 2 hours into the rhIGF-I infusion, and were suppressed until the subjects consumed a standard lunch (4 hours into the infusion). Insulin levels demonstrated a similar response to rhIGF-I, but decreases in insulin levels occurred after the rhIGF-I hypoglycemic effect. Therefore, suppression of insulin levels may be due to hypoglycemia rather than a direct action of rhIGF-I. This trial demonstrated the desired rhIGF-I effect of lowering subjects' glucose levels without clinically significant hypoglycemia. This finding suggests that rhIGF-I may have potential clinical utility in hyperglycemic or insulin resistant states.

Adult↗
PubMed1993

A novel ryanodine sensitive calcium release mechanism in cultured human myometrial smooth-muscle cells.

In cultured human myometrial cells application of caffeine (1-30 mM) did not result in an elevation of intracellular Ca2+ ([Ca2+]i). Caffeine was found to reversibly inhibit both spontaneous and agonist-induced repetitive rises in [Ca2+]i possibly as a consequence of its ability to interfere with the binding of inositol trisphosphate (IP3) to the receptor on the sarcoplasmic reticulum. Brief applications of ryanodine (1-10 microM) were observed to elevate [Ca2+]i and repeated exposures to ryanodine could elicit Ca2+ transients of similar magnitude. Ryanodine was also observed to mobilise Ca2+ in cells bathed in nominally Ca(2+)-free solution. These observations suggest the presence of a novel type of ryanodine-sensitive Ca(2+)-induced Ca2+ release (R-CICR) system in human myometrial cells.

Adult↗
PubMed1993

Dequalinium: a potent inhibitor of apamin-sensitive K+ channels in hepatocytes and of nicotinic responses in skeletal muscle.

The bisquaternary compound dequalinium has been tested for its ability to inhibit the loss of K+ which angiotensin II causes in guinea-pig hepatocytes and which occurs through apamin-sensitive Ca(2+)-activated K+ (SKCa) channels. Dequalinium blocked angiotensin II-evoked K+ loss with an IC50 of 1.5 +/- 0.1 microM and also inhibited 125I-monoiodoapamin binding with a KI of 1.1 +/- 0.1 microM. It is the most active non-peptide SKCa blocker so far described. The neuromuscular blocking agent vecuronium was also tested, and proved to be considerably less effective (IC50, 4.5 +/- 0.3 microM; KI, 3.6 +/- 0.5 microM). Dequalinium was also examined for its actions at nicotinic receptors in skeletal muscle and was found to be a potent, non-competitive antagonist of carbachol contractions of the frog rectus abdominis. In the frog cutaneous pectoris muscle, end-plate depolarizations induced by carbachol became smaller and more transient in the presence of dequalinium at 10 nM. However, contractions of the frog sartorius and rat diaphragm in response to nerve stimulation were inhibited only by concentrations > 1 microM. These apparently discrepant effects of dequalinium on nicotinic responses could be explained either by open channel block of slow onset or by 'stabilization' of the desensitized state of the receptor. The potency of dequalinium will make it a useful agent for the study of nicotinic receptors as well as of SKCa channels.

Angiotensin II↗
PubMed1993

Hypoglycemic and insulin response to a continuous intravenous infusion of CGP-35126 recombinant human insulin-like growth factor-I (rhIGF-I) in healthy males.

Recombinant human insulin-like growth factor-I (rhIGF-I) produced by expression in a yeast vector was evaluated in seven normal men to determine effects on plasma glucose and insulin levels. Each subject received an initial intravenous infusion of normal saline and on the following day, rhIGF-I at a rate of 21.4 micrograms/kg/hour. Each infusion lasted for 7 hours. The subjects' fasting baseline glucose and insulin levels were not statistically different (P > .05) from their pre-dose levels. Compared with the saline (control) infusion, serum glucose levels were statistically lower (P < .05) 2 hours into the rhIGF-I infusion. These lower glucose levels were maintained until the subjects consumed a standard lunch (4 hours into the infusion). Insulin levels demonstrated a similar response to rhIGF-I, but decreases in insulin levels occurred after the rhIGF-I hypoglycemic effect. This observation suggests that suppression of insulin levels may be due to secondary hypoglycemia rather than to a direct rhIGF-I effect. This study demonstrated the desired rhIGF-I effect of lowering subjects' glucose levels without clinically significant hypoglycemia. This finding suggests that rhIGF-I may have potential clinical utility in hyperglycemic states.

Adult↗
PubMed1993

Uricosuric effect of CGS-12970, a new thromboxane synthase inhibitor.

3-Methyl-2-(3-pyridyl)-1-indoleoctanoic acid (CGS-12970) is a reversible thromboxane synthase inhibitor that was noted to lower serum uric acid during preliminary trials in humans. Our clinical research unit studied 20 healthy male volunteers who received two doses of CGS-12970 12 hours apart (100, 200, 300, or 400 mg twice a day). Four subjects received placebo as a control. Serum uric acid concentrations decreased between 34% and 47%. Urinary excretion of uric acid increased between 28% and 134% within 12 hours of the first dose. Urinary excretion of uric acid returned to baseline within 24 hours after the last dose. In vitro study of bovine-creme xanthine oxidase inhibitor activity revealed minimal inhibition of xanthine oxidase by either CGS-12970 or its metabolite, CGS-12961. CGS-12970 appears to be a potent reversible uricosuric agent. We hypothesize that the uricosuric effect may be attributable to the acidic properties of CGS-12970 rather than to its inhibition of thromboxane synthase.

Adolescent↗
PubMed1993

Measurements of intracellular Ca2+ in cultured human myometrial smooth muscle cells bathed in low Na+ solutions.

In cultured human myometrial smooth muscle cells, removal of external Na+ activates repetitive increases in intracellular Ca2+ ([Ca2+]i). The Ca2+ transients persist in isotonic K+ solutions which suggests that the activity does not arise from regenerative changes in membrane potential. In nominally Ca(2+)-free solution, the activity disappears after a few cycles suggesting the involvement of internal stores. On Na+ removal, a background influx of Ca2+ may be responsible for activating the cyclical release of Ca2+ from internal stores. The absence of any effect of caffeine on resting [Ca2+]i suggests that the classical cardiac type of Ca(2+)-induced-Ca(2+)-release mechanism is not operating in these cells.

Adult↗
PubMed1993

The safety of the Esmarch tourniquet.

The use of an Esmarch bandage as a tourniquet in surgery has been criticized. Many authors claim that the pressures under the Esmarch are inconsistent and may be extremely high. We have seen few, if any, problems from the use of an Esmarch in surgery of the foot and ankle. The purpose of this study was to evaluate the pressures generated under the Esmarch tourniquet in a situation that mimics its clinical application, and to determine whether pressures of appropriate magnitude and consistency are obtained in order to recommend its continued use in surgery. Ten volunteers performed numerous applications of the Esmarch. The number of wraps and the width of the Esmarch bandage used were varied. The Esmarch was applied as it would be for a surgical case. Pressures directly beneath the Esmarch were recorded 8 cm proximal to the distal tip of the medial malleolus. Considering all volunteers and all pressures generated, a 3-in Esmarch applied with three wraps gave a mean pressure (+/- SD) of 225 +/- 46 mm Hg. A 3-in Esmarch applied with four wraps gave a mean pressure of 291 +/- 53 mm Hg. A 4-in Esmarch applied with three wraps gave a mean pressure of 233 +/- 35 mm Hg, and a 4-in Esmarch with four wraps gave a mean pressure of 284 +/- 42 mm Hg. The maximum pressures generated by any individual were as follows: 3-in three wraps, 321 mm Hg; 3-in four wraps, 413 mm Hg; 4-in three wraps, 328 mm Hg; and 4-in four wraps, 380 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)

Bandages↗