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Biomedical subjects

W McBride

Publications and source records attributed to W McBride.

At least 19 recordsLinked to original sources
PubMed1995

Resistance to common viruses during intralymphatic injections of tumor cell vaccines. Correlation with circulating cytokines.

Patients with advanced malignancies who received intralymphatic injections of irradiated tumor cell suspensions ("vaccines") were unexpectedly found to be resistant to common viral diseases; 17 patients with a documented past history of viral infections who have been observed for 48 to 148 months (median 108 months), were analyzed. The resistance to viruses was found to correlate closely with the presence, in the serum, of certain cytokines. Specifically, the interleukins, -2, -6, -8 and interferon-gamma, at low but sustained levels appeared to be possibly responsible for the nonspecific protection against viral infections obtained by intralymphatic injections of cellular material. These findings suggest that viral infections in normal or immunosuppressed individuals at particular risk might be prevented by treatments aimed at attaining very modest levels of certain cytokines.

Adult↗
PubMed1991

Production of tumor necrosis factor alpha and interferon gamma in interleukin-2-treated melanoma patients: correlation with clinical toxicity.

Interleukin-2 (IL-2)-based immunotherapy regimens are accompanied by dose-limiting toxicity consisting of fever, tachycardia, chills and capillary leak syndrome. We hypothesized that the toxicity was caused by the induction and release of endogenous cytokines such as tumor necrosis factor alpha (TNF alpha) and interferon gamma (IFN gamma). We measured the serum levels of TNF alpha and IFN gamma in IL-2-treated melanoma patients and attempted a correlation with clinical toxicity. A total of 23 patients received either 6 x 10(6) IU or 12 x 10(6) IU Cetus IL-2/m2 by i.v. bolus daily for 5 consecutive days on weeks 1, 3 and 5. Serum TNF alpha and IFN gamma levels were measured by enzyme-linked immunosorbent assay. Clinical toxicity was scored each day by objective measurements of hypotension, tachycardia, fever and chills/rigors. Clinical toxicity and IFN gamma levels correlated nicely, peaking on the 5th day of each treatment cycle. The kinetics and magnitude of TNF alpha production, however, were not predictable and did not correlate with either IFN gamma or toxicity. Some patients had modest increases in TNF alpha production while others had markedly increased levels during the second and third treatment weeks. Remarkably, these high levels persisted during nontreatment weeks and after completion of therapy. This clinical study demonstrates novel kinetics for immunoreactive TNF alpha in IL-2 cancer patients, which do not correlate well with toxicity.

Humans↗
PubMed1990

Potentiation of cocaine-induced coronary vasoconstriction by beta-adrenergic blockade.

STUDY OBJECTIVE: To determine whether beta-adrenergic blockade augments cocaine-induced coronary artery vasoconstriction. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: A cardiac catheterization laboratory in an urban teaching hospital. PATIENTS: Thirty clinically stable patient volunteers referred for catheterization for evaluation of chest pain. INTERVENTIONS: Heart rate, arterial pressure, coronary sinus blood flow (by thermodilution), and epicardial left coronary arterial dimensions were measured before and 15 minutes after intranasal saline or cocaine administration (2 mg/kg body weight) and again after intracoronary propranolol administration (2 mg in 5 minutes). MEASUREMENTS AND MAIN RESULTS: No variables changed after saline administration. After cocaine administration, arterial pressure and rate-pressure product increased; coronary sinus blood flow fell (139 +/- 28 [mean +/- SE] to 120 +/- 20 mL/min); coronary vascular resistance (mean arterial pressure divided by coronary sinus blood flow) rose (0.87 +/- 0.10 to 1.05 +/- 0.10 mm Hg/mL.min); and coronary arterial diameters decreased by between 6% and 9% (P less than 0.05 for all variables). Subsequently, intracoronary propranolol administration caused no change in arterial pressure or rate-pressure product but further decreased coronary sinus blood flow (to 100 +/- 14 mL/min) and increased coronary vascular resistance (to 1.20 +/- 0.12 mm Hg/mL.min) (P less than 0.05 for both). CONCLUSIONS: Cocaine-induced coronary vasoconstriction is potentiated by beta-adrenergic blockade. Beta-adrenergic blocking agents probably should be avoided in patients with cocaine-associated myocardial ischemia or infarction.

Adrenergic beta-Antagonists↗
PubMed1990

Alterations in left ventricular relaxation during atrioventricular pacing in humans.

To determine whether the asynchronous left ventricular contraction-relaxation sequence that exists during right ventricular pacing alters left ventricular relaxation, measurements of both the maximal rate of decline of left ventricular pressure (peak negative dP/dt) and the time constant of left ventricular relaxation were obtained during atrial and atrioventricular (AV) pacing in 25 patients referred for diagnostic cardiac catheterization. Heart rate was maintained at 10 to 15 beats/min above the sinus rate at rest, and relaxation was assessed during atrial pacing, AV pacing and repeat atrial pacing. The patients were classified into two groups. Group 1 included 10 patients with normal left ventricular systolic function at rest (ejection fraction greater than 0.55) and without evidence of prior myocardial infarction. Group 2 included 15 patients with a depressed left ventricular ejection fraction or akinesia of one or more left ventricular segments on the contrast ventriculogram, or both. Heart rate, peak left ventricular systolic pressure, end-systolic pressure and end-diastolic pressure remained constant during atrial, AV pacing and repeat atrial pacing in all patients. In group 1 patients, the decrease in peak negative dP/dt (1,507 +/- 200 versus 1,424 +/- 187 mm Hg/s) and the increase in the time constant of left ventricular relaxation (48 +/- 11 versus 51 +/- 11 ms) during AV pacing was not significantly different when compared with values during atrial pacing.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

Prevalence and clinical characteristics of a high cardiac output state in patients with multiple myeloma.

PURPOSE: This study was undertaken to define the prevalence and clinical characteristics of patients with a high cardiac output state associated with multiple myeloma. PATIENTS AND METHODS: Specifically, we evaluated clinical, laboratory, and two-dimensional and Doppler echocardiographic data in 36 patients with multiple myeloma. Cardiac output was determined noninvasively by a pulsed Doppler technique. RESULTS: A high cardiac output state, defined as a cardiac index greater than or equal to 4.0 L/minute/m2, was present in eight of 34 (23.5%) subjects in whom cardiac output was measurable. None of the known causes of high output states could be identified in these patients. Four patients developed high output congestive heart failure, two of whom died. Age, sex, degree of anemia, serum calcium level, immunoglobulin type, or disease stage did not differ significantly between subjects with or without high output states. However, severe bone involvement was significantly more frequent in those patients with high cardiac output states, occurring in all eight patients with high cardiac indexes compared with nine of 26 patients with low or normal cardiac indexes (p = 0.001). CONCLUSION: These data demonstrate that high cardiac output states are relatively common in patients with multiple myeloma and are associated with the presence of extensive bone disease.

Bone and Bones↗
PubMed1990

Human arylamine N-acetyltransferase genes: isolation, chromosomal localization, and functional expression.

N-Acetylation by hepatic arylamine N-acetyltransferase (NAT, EC 2.3.1.5) is a major route in the metabolism and detoxification of numerous drugs and foreign chemicals. NAT is the target of a common genetic polymorphism of clinical relevance in human populations. We have used our recently isolated rabbit cDNA rnat to clone three human NAT genes from human leukocyte DNA. None of the three genomic coding sequences was interrupted by introns. Two genes, designated NAT1 and NAT2, each possessed open reading frames of 870 bp. Both genes have been assigned to human chromosome 8, pter-q11. Following transfection they were transiently expressed in monkey kidney COS-1 cells. NAT1 and NAT2 gave rise to functional NAT proteins, as judged by their NAT enzyme activity with the arylamine substrate sulfamethazine. Western blots with NAT-specific antisera detected proteins of apparent molecular weight of 33 and 31 kD in NAT1- and NAT2-transfected cultures, respectively. The product of NAT2 had an identical apparent molecular weight as that of NAT detected in human liver cytosol. The deduced amino acid sequence of NAT2 also contained 6 peptide sequences which had previously been determined from tryptic peptides of the polymorphic NAT purified from human liver. These data suggest that NAT2 encodes the polymorphic NAT protein. The third gene, NATP, had multiple deleterious mutations and did not encode a functional NAT protein; it most likely represents a pseudogene.

Acetyltransferases↗
PubMed1990

Quantification of changes in serotonin uptake with spinal cord injury.

The high-affinity uptake of [3H]serotonin was studied using spinal cord preparations obtained from normal dogs, dogs made paraplegic by midthoracic transection, and dogs made monoplegic by midthoracic hemisection. Measurements were made at 1, 4, and 8 weeks after surgery. Lumbar spinal cord was removed at the above time periods and a myelin-free synaptosomal fraction was obtained by centrifugation and used for studying high-affinity serotonin uptake. At 1 week, there were no significant differences for Km values (nM) among any of the three groups (138 +/- 20, 128 +/- 22, and 118 +/- 20). The Vmax values (pmol/min/mg of protein) at 1 week for the control group (4.9 +/- 0.6) versus the hemisected group (4.3 +/- 0.7) were not significantly different. The Vmax values at 1 week for the completely transected group (2.3 +/- 0.3; P less than 0.01) were significantly reduced by 53 +/- 7%. At 4 weeks, the Vmax values for the hemisected (1.8 +/- 0.2; P less than 0.05) and transected groups (0.6 +/- 0.2; P less than 0.05) were significantly different as compared to the control group. The mean percent drop in Vmax after hemisection was 56 +/- 4%, close to the predicted value of 50%. The mean percent drop in Vmax after transection was 86 +/- 2%. At 8 weeks the mean Vmax values for the hemisected (1.9 +/- 0.3; P less than 0.05) and transected (0.4 +/- 0.4; P less than 0.05) groups were not significantly different compared to their respective 4-week values. It appears that serotonin uptake can be used to quantitate roughly the degree of spinal cord injury.

Animals↗
PubMed1990

Entrainment onset in a pacemaker model of reentrant ventricular tachycardia: insight into localization of critical elements of a reentrant circuit.

We investigated entrainment in a pacemaker model of reentrant ventricular tachycardia (VT) created in the intact dog heart using a VAT pacemaker with both electrodes on the ventricular epicardium. This produced an incessant wide QRS tachycardia originating from the pacing site with a cycle length equal to the conduction time between the sensing and pacing site plus the pacemaker AV delay. The conduction time between entrainment sites and the critical elements of the reentrant pathway (sensing and pacing sites) was determined by pacing at a comparable cycle length during sinus rhythm. Entrainment was achieved in 12 tachycardias with pacing at 1-4 sites at cycle lengths 10-100 msec shorter than tachycardia and confirmed by constant QRS fusion, progressive QRS fusion, and coupling of the first nonpaced QRS or intracardiac electrogram at the entraining cycle length. By least squares regression, the timing of entrainment onset (first reset of pacing or sensing site electrogram) measured by the prematurity of the local electrogram at the entraining site was highly correlated to the shortest conduction time between the entraining site and the circuit (F value of 84.7 and R = 0.752 [P less than 0.001]). Therefore, the timing of entrainment onset maybe useful in predicting the conduction time from the entraining site to critical elements of a reentrant circuit and may assist in localization of the reentrant pathway.

Animals↗
PubMed1990

Entrainment onset in atrioventricular reciprocating tachycardia: value in bypass tract localization and relationship to the preexcitation index.

The timing of entrainment onset has been shown to correlate with the conduction time to critical elements of a tachycardia circuit in a pacemaker model of reentrant ventricular tachycardia (VT). The utility of this method in evaluating clinical reentrant tachycardias was therefore evaluated in 24 patients with symptomatic Wolff-Parkinson-White syndrome and single bypass tracts (left free wall in 17, posteroseptal in 5, anteroseptal in 1, and right free wall in 1). Right ventricular apex (RVA) pacing during orthodromic atrioventricular reentrant tachycardia (oAVRT) at 10-70 msec less than tachycardia cycle length demonstrated concealed entrainment of the tachycardia in all patients studied. An entrainment index (EI), defined as the minimal prematurity of the ventricular stimulus that first resulted in atrial reset, was calculated from multiple entrainments in each patient. The EI was 121 +/- 25, 83 +/- 19, and 55 msec for left free wall, septal, and right free-wall bypass tracts, respectively (P = 0.004 for difference between left free wall and septal). A corrected EI, derived by subtracting the amount of atrial reset from the EI, gave values of 108 +/- 22 and 71 +/- 17 msec for left free wall and septal bypass tracts (P = 0.001). These values were compared to the preexcitation index (PI) by linear regression analysis in these patients. The PI correlated closely with both the EI and the corrected EI (r = 0.90 and 0.93, respectively), but the PI could only be derived in 12/17 (71%) left free-wall tachycardias versus the EI in 17/17 (100%) (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Pacing, Artificial↗
PubMed1989

Cocaine-induced coronary-artery vasoconstriction.

Intranasal cocaine is used frequently as a local anesthetic during many rhinolaryngologic procedures. Although its "recreational" use in high doses has been associated with chest pain and myocardial infarction, this association has not been established when cocaine is used in low doses as a topical anesthetic, and its effect on the coronary vasculature of humans is unknown. We studied the effects of intranasal cocaine (10 percent cocaine hydrochloride; 2 mg per kilogram of body weight) on the blood flow in and dimensions of the coronary arteries and on myocardial oxygen demand in 45 patients (34 men and 11 women, 36 to 67 years of age) who were undergoing cardiac catheterization for the evaluation of chest pain. Heart rate, arterial pressure, blood flow in the coronary sinus (measured by thermodilution), and the dimensions of the epicardial left coronary artery (measured by quantitative arteriography) were measured before and 15 minutes after the intranasal administration of saline (in 16 patients) or cocaine (in 29). No variables changed after the administration of saline. After cocaine was administered, the heart rate and arterial pressure rose, the coronary-sinus blood flow fell (from a mean [+/- SD] of 149 +/- 59 ml per minute to 124 +/- 53 ml per minute), and the diameter of the left coronary artery decreased by 8 to 12 percent (P less than 0.01 for all comparisons). No patient had chest pain or electrocardiographic evidence of myocardial ischemia after the administration of cocaine. Subsequently, the administration of the alpha-adrenergic blocking agent phentolamine caused all these values to return to base-line levels. There was no difference in response between the patients found to have disease of the left coronary artery (n = 28) and those without such disease (n = 17). We conclude that the intranasal administration of cocaine near the dose used for topical anesthesia causes vasoconstriction of the coronary arteries, with a decrease in the coronary blood flow, despite an increase in myocardial oxygen demand, and that these effects are mediated by alpha-adrenergic stimulation. It is reasonable to assume that these effects would be more pronounced at the much higher doses associated with the recreational use of cocaine.

Administration, Intranasal↗
PubMed1989

Low-level exposures to lead: the Sydney lead study.

The Sydney Lead Study is a prospective investigation of the relationship between low-level lead exposure and neurobehavioural development during the first five years of life. Of the initial cohort of 318 children, 207 remained at the end of the fourth year. Average blood lead levels at 42 and 48 months were 10.7 and 10.1 micrograms/dl, respectively, with only a minority of observations exceeding 15 micrograms/dl. The regression analyses support earlier findings from the study, in that exposure to lead resulting in the range of blood lead levels found in this cohort is not associated with mental or motor deficits in the preschool years.

Adult↗
PubMed1988

A human protein specific for the immunoglobulin octamer DNA motif contains a functional homeobox domain.

The homeobox domain is shared by Drosophila homeotic proteins, yeast mating type proteins, and some functionally uncharacterized mammalian proteins. A lymphoid-restricted human protein that binds to the immunoglobulin octamer regulatory motif was shown to contain an amino acid sequence that has 33% amino acid identity with the consensus sequence of the previously cloned homebox domains. This homeobox gene was localized to chromosome 19, thus mapping separately from other human homebox genes. A mutant protein containing amino acid substitutions within a putative helix-turn-helix motif in the homeobox domain did not bind DNA detectably. This human homeobox protein was shown to bind the same DNA sequence as the homeobox domains of the yeast mating type proteins and Drosophila homeotic protein, suggesting that homeobox proteins may have closely related DNA binding characteristics.

Amino Acid Sequence↗