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Biomedical subjects

C J Carter

Publications and source records attributed to C J Carter.

At least 55 records · Page 3Linked to original sources
PubMed1988

Reduced platelet count as a risk factor for intraventricular hemorrhage.

The role of thrombocytopenia as a risk factor for intraventricular hemorrhage in infants of very low birth weight is unclear. This study investigates the relationship between the lowest platelet count and the occurrence of intraventricular hemorrhage in 302 consecutively admitted infants with birth weights under 1500 g. Intraventricular hemorrhage, which occurred in 90 infants (29.8%), was correlated with the lowest platelet count obtained during the first 4 days of life. In 27 infants with intraventricular hemorrhage, the lowest platelet count was less than 100 X 10(9)/L. Statistical analysis of the data demonstrated that reduced platelet count was not associated significantly with intraventricular hemorrhage. Similarly, the severity of intraventricular hemorrhage did not correlate with the lowest platelet count. These data suggest that a reduced platelet count does not play a major role in the pathogenesis of intraventricular hemorrhage in infants of very low birth weight.

Asphyxia Neonatorum↗
PubMed1988

Heparin therapy for venous thrombosis and pulmonary embolism.

Intravenous heparin is the initial treatment of choice for most patients with acute pulmonary embolism or proximal deep vein thrombosis. The primary objective of initial heparin therapy in such patients is to prevent recurrent venous thromboembolism. The efficacy of intravenous heparin for this purpose has been established by randomized clinical trials in patients with pulmonary embolism, and more recently, in patients with proximal vein thrombosis. Heparin is given as an initial intravenous bolus of 5000 units, followed by a maintenance dose of 30,000-40,000 units per 24 h by continuous intravenous infusion. A recent randomized trial in patients with proximal vein thrombosis indicates that failure to achieve an adequate anticoagulant response (APTT greater than 1.5 times control) is associated with a high risk (25%) of recurrent venous thromboembolism. Intravenous heparin administered in doses that prolong the activated partial thromboplastin time (APTT) to 1.5 or more times the control value is highly effective, and associated with a low frequency (2%) of recurrent venous thromboembolism. Heparin is continued for 7-10 days, overlapped with warfarin sodium during the last 4-5 days. Multiple randomized clinical trials indicate that this approach is highly effective. An alternative approach is to commence heparin and oral anticoagulants together at the time of diagnosis, and to discontinue heparin on the fourth or fifth day. A recent randomized trial in patients with submassive venous thrombosis or pulmonary embolism suggests that 4-5 days of initial heparin therapy is effective and safe, but this approach must be evaluated by further randomized trials before it is recommended for patients with extensive proximal vein thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Heparin↗
PubMed1988

Differential control by N-methyl-D-aspartate and kainate of striatal dopamine release in vivo: a trans-striatal dialysis study.

Using the technique of trans-striatal dialysis in halothane-anesthetized rats, we have studied the effects of intrastriatally infused N-methyl-D-aspartate (NMDA), kainate, and quisqualate on the liberation of endogenous striatal dopamine. The striatal infusion of NMDA (10(-3)-10(-2) M) or kainate (10(-4)-10(-2) M) but not of quisqualate (up to 10(-2) M) for one 20-min fraction provoked a dramatic increase in striatal dopamine efflux up to a maximum of 1,200 and 3,400% of basal levels for NMDA and kainate, respectively. NMDA (10(-3) M) evoked liberation of striatal dopamine was totally blocked by coinfusion of 2-amino-5-phosphonovalerate (2-APV; 5 X 10(-4) M) and by the systemic injection of phencyclidine (3 mg/kg i.p.). The effects of NMDA (10(-3) M) were also totally antagonized in a dose-dependent manner by the striatal coinfusion of atropine (10(-7)-10(-4) M), and abolished in rats that had received bilateral striatal ibotenate lesions (10 micrograms/1 microliter) 1 week prior to implantation of the dialysis fiber. The striatal infusion of tetrodotoxin (10(-6) M) reduced basal dopamine efflux by 60-70% and abolished the NMDA (10(-3) M)-evoked liberation of striatal dopamine. The effects of kainate (10(-3) M) on striatal dopamine efflux were only partially reduced by doses of 2-APV or atropine that totally blocked the NMDA response, and were also partially resistant to tetrodotoxin.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1988

Noradrenaline antagonizes and ouabain potentiates the effects of N-methyl-D-aspartate on rat cerebellar cyclic GMP production.

Noradrenaline potently antagonizes the effects of N-methyl-D-aspartate (NMDA) (80 microM) on cyclic GMP production in immature rat cerebellar slices in vitro (IC50 = 0.6 microM). The effect is stereospecific (D-noradrenaline, IC50 = 100 microM), and also observed with adrenaline (IC50 = 0.5 microM) and isoprenaline (IC50 = 1.2 microM). The alpha 1-adrenoceptor agonists methoxamine or phenylephrine or the mixed alpha 1/alpha 2 agonists oxymetazoline or xylometazoline (100 microM) do not block the effects of NMDA, but the alpha 2-adrenoceptor agonist clonidine is weakly active (IC50 = 200 microM). Salbutamol and terbutaline were also inactive except at high concentrations (300 microM), as were a number of other catechol and phenylethylamine derivatives. The antagonistic effects of noradrenaline on the NMDA response were insensitive to phentolamine, atenolol, or propranolol (up to 100 microM), but were blocked by the alpha 2 antagonist idazoxan (1-10 microM). The Na+,K+-ATPase inhibitor ouabain (0.1-10 microM) markedly potentiates the effects of NMDA in this model, and also antagonizes and reverses the ability of noradrenaline (10 microM) to block the effects of NMDA. The results suggest that noradrenaline and Na+,K+-ATPase activity have potent modulatory effects on the NMDA response.

Animals↗
PubMed1988

Antithrombin-III-Hamilton: a gene with a point mutation (guanine to adenine) in codon 382 causing impaired serine protease reactivity.

Antithrombin-III-Hamilton is a structural mutant of antithrombin III with defective serine protease reactivity, demonstrable in three members of a French Canadian family. The propositus, a 54-year-old man with a history of recurrent thromboembolic events, and his two asymptomatic grown children are heterozygous for the mutant antithrombin III gene. In all three individuals, the immunoreactive antithrombin III level is normal, while the antithrombin and antifactor Xa activity is approximately 50% of the control value. Two dimensional immunoelectrophoresis of antithrombin-III-Hamilton in the presence of heparin is normal. Purified antithrombin-III-Hamilton did not form thrombin-antithrombin III complex when incubated with thrombin for up to 30 minutes. The normal and mutant antithrombin III alleles of the propositus could be distinguished by linkage to Pstl restriction fragment length polymorphisms (RFLP). Genomic DNA from the propositus was cloned into EMBL 3 phage vectors and two clones containing nearly complete copies of the antithrombin-III-Hamilton allele were identified. Exon 6 of both clones was subcloned into M13 phage vector and sequenced, revealing a G----A point mutation in the first base of codon 382. Codon 382 codes for alanine in the normal allele and for threonine in the antithrombin-III-Hamilton allele. Alanine-382, 12 residues from the reactive center, is a highly conserved amino acid in the family of serine protease inhibitors known as the serpins. We postulate that, as a result of the substitution of threonine for alanine in antithrombin-III-Hamilton, either the tertiary structure or the hydrophobicity of the thrombin-binding region is altered, causing aberrant conformation of the Arg-393-Ser-394 bond at the reactive center impairing the interaction between antithrombin-III-Hamilton and the activated serine proteases.

Alleles↗
PubMed1988

A comparison of seven prothrombin time reagents--development of an evaluation strategy.

The control of p.o. anticoagulant therapy by the use of prothrombin times or ratios is one of the major functions of a clinical coagulation laboratory. European prothrombin reagents tend to be more sensitive to the effects of p.o. anticoagulants than traditional North American rabbit brain thromboplastin reagents. The clinical importance of this in vitro observation has been emphasized by the results of two recent clinical trials which both suggested that the less intense anticoagulation therapy that results from the use of a European-type prothrombin reagent may be safer. To minimize the clinical effects of differences in prothrombin time reagent formulation, a global correction factor has been developed--the international normalized ratio (INR). Despite this advance in international standardization, individual laboratories need a rapid and efficient method to help select the most appropriate prothrombin reagent for the clinical management of their local patient population. This study has examined the response of a variety of commercially available prothrombin time reagents to normal plasmas and those from anticoagulated patients. Using both classical sampling theory and multiple range testing, it was demonstrated that as few as 20 estimations on normal plasmas and 50 on anticoagulated specimens will permit a clinical laboratory to select a suitable prothrombin time reagent for anticoagulant control of their specific local patient population.

Anticoagulants↗
PubMed1988

Pulmonary embolism in outpatients with pleuritic chest pain.

Pleuritic chest pain is a frequent complaint in patients coming to the emergency room, but the proportion of such patients with pulmonary embolism is uncertain. In a prospective study, we evaluated the diagnostic outcomes in 173 consecutive patients who came to the emergency room with pleuritic chest pain. Pulmonary embolism, as demonstrated by angiography or autopsy, was present in 36 (21%). The need for objective testing is clearly indicated by our finding that the sensitivity (85%) and specificity (37%) of predetermined clinical variables for pulmonary embolism were insufficient to allow a definitive treatment decision. Optimal sensitivity and specificity are obtained by using pulmonary angiography in combination with lung scanning. The proportion of patients requiring angiography is substantially reduced, from 43% to 26%, without significant loss of accuracy, if ventilation imaging and impedance plethysmography are used together with perfusion scanning.

Adult↗
PubMed1987

Raised extracellular potassium relieves the blockade by magnesium of NMDA-induced cerebellar cyclic GMP production.

In magnesium-containing Krebs buffer raised extracellular potassium increases the effects of NMDA on cyclic GMP production in immature rat cerebellar slices in vitro. This effect is not seen in magnesium-free buffer. The interaction between magnesium and potassium ions has competitive kinetics and the blockade of the NMDA channel by magnesium is surmountable by potassium. The inhibitory potency of magnesium on the NMDA receptor channel complex can thus be regulated by extracellular potassium levels. This may explain the unmasking of NMDA receptors in high frequency stimulation and their involvement in epilepsy and ischaemia, conditions in which synaptic potassium levels are elevated.

Animals↗
PubMed1987

Double-blind randomised trial of Org 10172 low-molecular-weight heparinoid in prevention of deep-vein thrombosis in thrombotic stroke.

In a double-blind, randomised trial Org 10172 low-molecular-weight (LMW) heparinoid was compared with placebo in the prevention of deep-vein thrombosis in patients with acute thrombotic stroke. Prophylaxis was started within 7 days of the onset of stroke with a loading dose of 1000 anti-factor-Xa units intravenously followed by a fixed dose of 750 anti-factor-Xa units twice a day subcutaneously; it was continued for 14 days or until hospital discharge, if earlier. 50 patients were randomised to receive Org 10172 and 25 to receive placebo. All patients underwent surveillance with I125-fibrinogen leg scanning and impedance plethysmography. Venography was carried out if either test became positive. Venous thrombosis occurred in 2 of 50 patients (4.0%) given Org 10172 and 7 of 25 patients (28.0%) given placebo (p = 0.005); the corresponding rates of proximal-vein thrombosis were 0% and 16%, respectively (p = 0.01). There was one major haemorrhage in the Org 10172 group and one minor bleed in the placebo group.

Acute Disease↗
PubMed1987

Ionic mechanisms implicated in the stimulation of cerebellar cyclic GMP levels by N-methyl-D-aspartate.

N-Methyl-D-aspartate (NMDA) increases cyclic GMP levels in immature rat cerebellar slices incubated in magnesium-containing Krebs buffer in vitro. This effect is blocked by 2-amino-5-phosphonovalerate and by D-alpha-aminoadipate, but not by glutamic acid diethyl ester or gamma-D-glutamylaminomethylsulfonic acid, indicating specific involvement of the NMDA receptor. The response produced by NMDA is abolished by removal of calcium from the medium, proportional to the concentration of extracellular calcium, and blocked by a number of inorganic (Ni2+, Co2+, Cd2+, La3+, Mn2+) calcium antagonists. The responses to NMDA are not blocked by barium or strontium and persist when these ions are substituted for calcium in the incubation medium. The effects of NMDA are blocked by, but are not particularly sensitive to, the organic voltage-dependent calcium channel antagonists. Nifedipine (10 microM) produces partial inhibition of the effects of NMDA, which are also antagonized by high (greater than 200 microM) concentrations of diltiazem and verapamil. The effects of NMDA are tetrodotoxin insensitive but are abolished by omission of sodium from the medium and inhibited by a tetrodotoxin-insensitive sodium channel blocker, Zn2+. The results suggest that calcium channel opening is a consequence of NMDA receptor activation in this model. However, the sodium dependence of the response argues against the use of receptor-operated calcium channels, whereas the weak activity of the organic voltage-sensitive calcium channel antagonists argues either against the use of voltage-dependent calcium channels, or that those implicated in the effects of NMDA are insensitive to these agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

2-Oxo-[14C]glutarate is taken up by glutamatergic nerve terminals in the rat striatum.

High affinity uptake of [14C]glutamate into rat striatal synaptosomes was reduced by 33% after bilateral cortical ablation. The lesion had no effect on striatal [14C]GABA uptake, but reduced 2-oxo-[14C]glutarate uptake by 67%. The results demonstrate the existence of a high-affinity uptake site for 2-oxoglutarate on glutamatergic nerve terminals and support the contention that this Krebs cycle intermediate may be used to replenish the neuronal pool of neurotransmitter glutamate. 2-Oxo-[14C]glutarate uptake may serve as a selective marker for glutamatergic neurones.

Animals↗
PubMed1986

A randomized controlled trial of a low-molecular-weight heparin (enoxaparin) to prevent deep-vein thrombosis in patients undergoing elective hip surgery.

There is experimental evidence that low-molecular-weight fractions of heparin are as effective as the standard form but cause less bleeding. We therefore performed a double-blind, randomized trial comparing PK10169 low-molecular-weight heparin with placebo for the prevention of venous thrombosis in patients undergoing elective hip surgery. Prophylactic treatment with a fixed dose was begun postoperatively and continued for 14 days. Fifty patients in each treatment group underwent surveillance with [125I]fibrinogen leg scanning and impedance plethysmography. In the first 24 patients, venography was performed only if either surveillance test was positive. Because the rate of venous thrombosis detected in those patients was unexpectedly low, venography was requested in the remaining 76 patients, even if the screening tests were negative. In this latter group, venous thrombosis occurred in 4 patients (10.8 percent) given PK10169 heparin and 20 patients (51.3 percent) given placebo (P = 0.0002); the corresponding rates for proximal-vein thrombosis were 5.4 percent and 23.1 percent, respectively (P = 0.029). In the entire group of 100 patients, venous thrombosis occurred in 12 percent of those given PK10169 heparin and 42 percent of those given placebo (P = 0.0007), and the corresponding rates for proximalvein thrombi were 4 percent and 20 percent, respectively (P = 0.014). The observed hemorrhagic rate was 4 percent in each treatment group. We conclude that prophylaxis with fixed-dose PK10169 heparin is effective and safe for patients undergoing elective hip replacement.

Aged↗
PubMed1985

Diagnostic value of ventilation-perfusion lung scanning in patients with suspected pulmonary embolism.

Differing opinions about the value of ventilation-perfusion lung scanning have created controversy concerning the correct approach to the diagnosis of pulmonary embolism. In a prospective study of 305 consecutive patients with clinically suspected pulmonary embolism and abnormal perfusion lung scans, we evaluated the role of ventilation-perfusion lung scanning, pulmonary angiography, and objective testing for venous thrombosis in the diagnostic process. Segmental or greater perfusion defects with ventilation mismatch have a high probability (86 percent) of pulmonary embolism. Contrary to current clinical practice, however, the approach of ruling against pulmonary embolism by a "low probability" scan pattern is incorrect, even with an improved technique for ventilation imaging; the frequency of pulmonary embolism in these patients ranged from 25 to 40 percent. Objective testing for venous thrombosis provides a practical alternative to performing pulmonary angiography in the diagnostic work-up; by providing an endpoint for commencing anticoagulant therapy, a positive result obviates the need for further testing in 20 to 30 percent of patients.

Adolescent↗
PubMed1985

In vivo activity of a new heparinoid.

Org 10172 is a heparinoid prepared during the manufacture of porcine mucosal heparin. This compound has been compared with a standard commercial grade heparin in vitro and in vivo using experimental thrombosis and bleeding models in rabbits. Increasing doses of both the heparin and the heparinoid resulted in a similar prolongation of a Xa clotting time and the APTT, but the heparinoid had no effect on the thrombin clotting time over the concentration range 0-3.0 units/ml. Both preparations were antithrombotic using a stasis prophylaxis model but inhibition of thrombosis was independent of the ex vivo anti-Xa heparin levels achieved. Relative to heparin, the heparinoid failed to induce hemorrhage. A potential therapeutic advantage for Org 10172 as an antithrombotic agent for clinical use can be predicted.

Animals↗
PubMed1985

Diagnostic efficacy of impedance plethysmography for clinically suspected deep-vein thrombosis. A randomized trial.

Impedance plethysmography is an accurate noninvasive method to test for proximal vein thrombosis, but it is insensitive to calf-vein thrombi. We randomly assigned patients on referral with clinically suspected deep-vein thrombosis and normal impedance plethysmographic findings to either serial impedance plethysmography alone or combined impedance plethysmography and leg scanning (which has been shown to be essentially as sensitive as venography) and compared the long-term outcomes. During the initial surveillance, deep-vein thrombosis was detected in 6 of 311 patients (1.9%) tested by serial impedance plethysmography alone and in 30 of 323 patients (9.3%) (most with calf-vein thrombi) tested by the combined approach (p less than 0.001). During long-term follow-up, no patient died from pulmonary embolism; but 6 patients (1.9%; 95% confidence limits, 0.7% to 4.2%) tested by serial impedance plethysmography developed deep-vein thrombosis compared with 7 patients (2.2%; 95% confidence limits, 0.9% to 4.4%) tested by the combined approach. Serial impedance plethysmography used alone is an effective strategy to evaluate such symptomatic patients.

Adult↗
PubMed1985

Activation and proliferation signals in mouse B cells. VI. Anti-Ig antibodies induce dose-dependent cell cycle progression in B cells.

Recent studies from several laboratories have shown that the concentrations of anti-immunoglobulin antibodies required to induce B lymphocytes to synthesize DNA are quite different from those needed to activate these cells, i.e. to cause resting B cells to leave G0. The present experiments examine this difference in detail. Thus, stimulation of DNA synthesis in mouse B cells requires prolonged (greater than 30 hr) exposures to high (greater than or equal to 10 micrograms/ml) concentrations of soluble F(ab')2 fragments of rabbit anti-Ig antibodies. However, as little as 50 ng/ml antibody caused B cells to enlarge, to express increased levels of Ia antigens, and to become primed to synthesize DNA more rapidly in response to restimulation with mitogenic concentrations of anti-Ig. The results of kinetic experiments suggested that the 'distance' that cells progress from G0 towards S depends not only on the time of exposure to anti-Ig, but also on its concentration. Concentrations of antibody less than 1 microgram/ml did not induce detectable RNA synthesis, and hence do not drive cells into the G1 phase of the cell cycle. Instead, under these conditions, B cells appear to enter a transitional, primed state (which has been termed GIT). This may well reflect the state into which T-dependent antigens drive resting B cells.

Animals↗
PubMed1984

Reduced GABA transaminase activity in the Huntington's disease putamen.

GABA transaminase activity is reduced in autopsied putamen samples from patients dying with Huntington's disease. Its activity is also reduced in the striatum of rats previously lesioned with kainic acid. In both cases, the reduction in GABA transaminase activity is comparable with the reduction in glutamate decarboxylase activity, supporting the suspected localization of this enzyme to GABA neurones within the basal ganglia.

4-Aminobutyrate Transaminase↗