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Biomedical subjects

G M Vincent

Publications and source records attributed to G M Vincent.

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

Locus heterogeneity of autosomal dominant long QT syndrome.

Autosomal dominant long QT syndrome (LQT) is an inherited disorder that causes syncope and sudden death from cardiac arrhythmias. In genetic linkage studies of seven unrelated families we mapped a gene for LQT to the short arm of chromosome 11 (11p15.5), near the Harvey ras-1 gene (H ras-1). To determine if the same locus was responsible for LQT in additional families, we performed linkage studies with DNA markers from this region (H ras-1 and MUC2). Pairwise linkage analyses resulted in logarithm of odds scores of -2.64 and -5.54 for kindreds 1977 and 1756, respectively. To exclude the possibility that rare recombination events might account for these results, we performed multipoint linkage analyses using additional markers from chromosome 11p15.5 (tyrosine hydroxylase and D11S860). Multipoint analyses excluded approximately 25.5 centiMorgans of chromosome 11p15.5 in K1756 and approximately 13 centiMorgans in K1977. These data demonstrate that the LQT gene in these kindreds is not linked to H ras-1 and suggest that mutations in at least two genes can cause LQT. While the identification of locus heterogeneity of LQT will complicate genetic diagnosis, characterization of additional LQT loci will enhance our understanding of this disorder.

Chromosome Mapping↗
PubMed1992

The spectrum of symptoms and QT intervals in carriers of the gene for the long-QT syndrome.

BACKGROUND: The familial long-QT syndrome is characterized by a prolonged QT interval on the electrocardiogram, ventricular arrhythmias, and sudden death. It is not certain, however, that the length of the QT interval is a sensitive or a specific diagnostic criterion. Recently, we identified genetic markers on chromosome 11 that distinguished between carriers and noncarriers of the gene for the long-QT syndrome in three families. In this study, we compared the clinical features of carriers and noncarriers and assessed the diagnostic accuracy of the QT interval. METHODS: We obtained medical histories and electrocardiograms from 199 family members. QT intervals corrected for heart rate (QTc) were determined independently by two blinded investigators. Carriers of the long-QT gene (83 subjects) and noncarriers (116 subjects) were distinguished by genetic-linkage analysis. RESULTS: Fifty-two of the carriers of the long-QT gene (63 percent) had a history of syncope, whereas four (5 percent) had a history of aborted sudden death. The QTc intervals of the gene carriers ranged from 0.41 to 0.59 second (mean, 0.49). By contrast, the QTc intervals of the noncarriers ranged from 0.38 to 0.47 second (mean, 0.42). On average, carriers of the gene for the long-QT syndrome had longer QTc intervals than noncarriers, but there was substantial overlap (in 126 of the 199 subjects, or 63 percent). The use of a QTc interval above 0.44 second as a diagnostic criterion resulted in 22 misclassifications among the 199 family members (11 percent). QTc intervals of 0.47 second or longer in males and 0.48 second or longer in females were completely predictive but resulted in false negative diagnoses in 40 percent of the males and 20 percent of the females. CONCLUSIONS: In families affected by the long-QT syndrome, measurement of the QTc interval may not permit an accurate diagnosis. DNA markers make it possible to make a genetic diagnosis in some families, but not all gene carriers have symptoms.

Adolescent↗
PubMed1992

Hypothesis for the molecular physiology of the Romano-Ward long QT syndrome.

OBJECTIVES: The aim of this review was to develop a hypothesis for the molecular pathophysiology of the inherited long QT syndrome. BACKGROUND: The pathophysiology of the long QT syndrome is unknown. An abnormality of the sympathetic nervous system has been suspected because of the slow heart rates observed and the common precipitation of syncope by adrenergic stimulation (exercise or fright). The characteristic QT prolongation and torsade de pointes arrhythmias suggest a potassium ion (K+) abnormality. Recent findings from molecular biology and genetic linkage analysis studies provide a basis for a new hypothesis that unifies these clinical manifestations. METHODS: Several recent studies regarding ras proteins were evaluated and correlated. Associations between ras proteins, G protein function and the known features of the long QT syndrome were identified. Based on these associations, a hypothesis for the molecular pathophysiology was developed. RESULTS: The Romano-Ward long QT phenotype is linked to the Harvey ras-1 gene on chromosome 11 in many, but not all, families. Ras genes exhibit G protein properties, acting as intermediaries in transmembrane signaling pathways including K+ and beta-adrenergic channels. Mutation of ras p21 protein significantly reduces the G protein function of the ras protein, thereby interfering with signal transduction. CONCLUSIONS: These various studies suggest that a mutation of the disease gene (not necessarily H-ras-1) alters the G protein function of the gene and interferes with delayed rectifier K+ and beta-receptor channel signaling. This hypothesis appears to explain and unify the several characteristic features of the long QT syndrome.

Animals↗
PubMed1991

Effects of exercise on heart rate, QT, QTc and QT/QS2 in the Romano-Ward inherited long QT syndrome.

Patients with the Romano-Ward inherited long QT syndrome have an incompletely defined cardiac sympathetic system abnormality, and exhibit ventricular arrhythmias during exercise, fear and anxiety. Treadmill and bicycle exercise were used to modulate cardiac autonomic activity in 27 Romano-Ward subjects and 27 normal controls. The heart rate, and the QT, QTc and QT/QS2 (ratio of electrical to mechanical systole) intervals were compared. Subjects with long QT were compared with normals. Those with a long QT interval had the following results: similar resting heart rates; lower rates during moderate (151.6 vs 169.6 beats/min, p = 0.04) and maximal (155.9 vs 182.1 beats/min, p = less than 0.001) exercise; an abnormal QT cycle-length relationship, with failure of the QT to shorten normally with increasing heart rate; an increase in QTc versus a decrease in normals; supine rest QT/QS2 ratio of 1.12 vs 0.93, p = 0.001; and an exercise QT/QS2 that increased by 30%, from 1.12 at rest to 1.45, versus 15%, in normals, from 0.93 to 1.07, p = 0.001. The lower heart rates and excessively prolonged QT/QS2 ratios during exercise further support an abnormality of, or abnormal cardiac response to, sympathetic activity. A QT/QS2 greater than 1.0 at rest, an exercise QT/QS2 ratio greater than 1.17, and an increase in QTc during moderate exercise may be helpful diagnostic findings in patients with borderline long QTc intervals at rest.

Adult↗
PubMed1991

Linkage of a cardiac arrhythmia, the long QT syndrome, and the Harvey ras-1 gene.

Genetic factors contribute to heart disease. In this study, linkage analyses have been performed in a family that is predisposed to sudden death from cardiac arrhythmias, the long QT syndrome (LQT). A DNA marker at the Harvey ras-1 locus (H-ras-1) was linked to LQT with a logarithm of the likelihood ratio for linkage (lod score) of 16.44 at theta = 0, which confirms the genetic basis of this trait and localizes this gene to the short arm of chromosome 11. As no recombination was observed between LQT and H-ras-1, and there is a physiological rationale for its involvement in this disease, ras becomes a candidate for the disease locus.

Chromosome Mapping↗
PubMed1991

Protamine allergy reactions during cardiac catheterization and cardiac surgery: risk in patients taking protamine-insulin preparations.

Protamine insulin use may immunologically sensitize patients to protamine, leading to anaphylactoid reactions upon subsequent exposure to protamine sulfate during cardiac catheterization or cardiovascular surgery. The risk of such reactions in protamine insulin-dependent patients is uncertain. One catheterization study reported a 50-fold greater risk while a second showed no increased risk! To clarify the risk, the records of 7,750 cardiac catheterization procedures between 1984 and 1987 were analyzed for presence of NPH or PZI insulin use, protamine administration, and any complications or adverse reactions. Protamine was administered in 3,341/7,750 procedures (43%), including 171 in diabetics receiving NPH insulin. Adverse reactions to protamine occurred in 2/3, 170 noninsulin patients, 0.06%, and adverse reactions due to probable NPH insulin sensitization occurred in 1/171, 0.6%, of NPH diabetics, p = .034. Meta-analysis of risk showed an odds ratio of 7.96 for the NPH diabetic patients, and combining these results with the other large series in the literature (269 NPH diabetics total) showed an odds ratio of 4.19 compared to a non-NPH insulin group. Meta-analysis of the surgical literature showed the risk in surgical patients to be 2.1% in NPH patients versus 0.12% with no NPH, with an odds ratio of 15.52. The greater incidence in surgical patients may be due to protamine sensitization at prior catheterization and to the larger dose of protamine administered to surgical patients.

Anaphylaxis↗
PubMed1991

Presence of blood significantly decreases transmission of 630 nm laser light.

Application of 630 nm light in the presence of blood is often necessary during photodynamic therapy, particularly for proposed intravascular applications. The effect of blood on transmission of 630 nm light was studied using a three dimensional irradiation model and an integrating sphere for measuring light transmitted in any direction through blood layers of different hematocrit (25 to 75) and thickness (.15 to .98 mm). There was an inverse relationship between transmission and hematocrit and transmission and blood thickness, p = .000 for both. At a physiologic hematocrit of 46, transmission through blood layers of .98, .41, .28, and .15 mm were 21%, 33%, 29%, and 58% respectively. These blood thicknesses or more are likely in the clinical environment, and can be expected to result in significant transmission losses. The marked absorption of 630 nm light by blood indicates that removal of the blood or correction for power loss should be employed when 630 nm light is applied in a blood containing environment.

Absorption↗
PubMed1991

In vivo canine coronary artery laser irradiation: photodynamic therapy using dihematoporphyrin ether and 632 nm laser. A safety and dose-response relationship study.

This study examined the safety and dose-response relationships of 632-nm laser irradiation of photosensitized normal coronary arteries in 27 dogs. Fifteen received 2.5 mg/kg dihematoporphyrin ether (DHE), seven received no sensitizer, and five had coronary instrumentation but no laser (sham laser procedures) at nine coronary sites--four sensitized, five non-sensitized. Laser energy of 82 to 1,640 J/cm2 was delivered via a 584 microns diffusing-tip optical fiber, providing estimated tissue fluences of 20 to 410 J/cm2. Serial electrocardiograms and selective coronary arteriograms were performed up to 1 month post laser irradiation. Histologic examination was performed of all treated sites. Tissue fluences less than 200 J/cm2 produced no permanent electrocardiographic or angiographic changes; reversible spasm occurred in 2/8 photosensitized-lased, 0/2 non-photosensitized-lased. Minor medial damage occurred in 1/8 sensitized-lased, 1/2 non-sensitized-lased, and 0/9 sham-lased sites. At tissue fluences greater than 200 J/cm2 4/7 sensitized-lased animals died prematurely--one due to immediate and irreversible coronary spasm and Q wave infarction, one due to fibrillation during 48-hour follow-up coronary angiography (normal angiograms), two with normal electrocardiograms and angiograms within one day of undetermined death; 0/5 non-sensitized-lased animals expired or had coronary spasm; and 3/7 sensitized-lased and 0/5 non-sensitized/lased had significant medial to adventitial histologic damage. Coronary irradiation at less than 200 J/cm2 appears to be safe for photodynamic treatment of atherosclerotic lesions. Pretreatment for coronary spasm is appropriate.

Angioplasty, Balloon, Coronary↗
PubMed1991

An evaluation of potential prognostic indicators in cardiac patients.

Cardiovascular disease results in more deaths and higher medical costs than any other medical problem. Cardiac patients may be transported to centers for specialized care. We evaluated historical, current event, and physiologic items (n = 32) for ability to predict use of specialized care and hospital costs. For 199 patients studied, seven items were prognostic. A model classifying patients by presence of predictors was developed. For the group without predictors and the group with multiple predictors, sensitivity and specificity were respectively very good. For 125 (63%) of the patients in middle categories, the model was not sufficiently sensitive to be prognostic. A scoring system for all cardiac patients could not be developed. Patients requiring only diagnostics were responsible for financial deficits, as were all Medicare patient groups. Patients staying longer than seven days, or having surgery, or both, were responsible for the largest deficits (if on Medicare) and the highest profits (if not on Medicare). Advance validation of the need to transport is difficult, with far-reaching medical and financial implications.

Adult↗
PubMed1991

The long QT syndrome. Prospective longitudinal study of 328 families.

BACKGROUND: The Long QT Syndrome (LQTS) is an infrequently occurring familial disorder in which affected individuals have electrocardiographic QT interval prolongation and a propensity to ventricular tachyarrhythmic syncope and sudden death. We prospectively investigated the clinical characteristics and the long-term course of 3,343 individuals from 328 families in which one or more members were identified as affected with LQTS (QTc greater than 0.44 sec1/2). METHODS AND RESULTS: The first member of a family to be identified with LQTS, the proband, was usually brought to medical attention because of a syncopal episode during childhood or teenage years. Probands (n = 328) were younger at first contact (age 21 +/- 15 years), more likely to be female (69%), and had a higher frequency of preenrollment syncope or cardiac arrest with resuscitation (80%), congenital deafness (7%), a resting heart rate less than 60 beats/min (31%), QTc greater than or equal to 0.50 sec1/2 (52%), and a history of ventricular tachyarrhythmia (47%) than other affected (n = 688) and unaffected (n = 1,004) family members. Arrhythmogenic syncope often occurred in association with acute physical, emotional, or auditory arousal. The syncopal episodes were frequently misinterpreted as a seizure disorder. By age 12 years, 50% of the probands had experienced at least one syncopal episode or death. The rates of postenrollment syncope (one or more episodes) and probable LQTS-related death (before age 50 years) for probands (n = 235; average follow-up 54 months per patient) were 5.0% per year and 0.9% per year, respectively; these event rates were considerably higher than those observed among affected and unaffected family members. CONCLUSIONS: Among 232 probands and 1,264 family members with prospective follow-up, three factors made significant independent contributions to the risk of subsequent syncope or probable LQTS-related death before age 50 years, whichever occurred first (Cox hazard ratio; 95% confidence limits): 1) QTc (1.052; 1.017, 1.088), 2) history of cardiac event (3.1; 1.3, 7.2), and 3) heart rate (1.017; 1.004, 1.031). The findings from this prospective longitudinal study highlight the clinical features, risk factors, and course of LQTS.

Adult↗
PubMed1991

Consistent linkage of the long-QT syndrome to the Harvey ras-1 locus on chromosome 11.

The long-QT syndrome (LQT; Ward-Romano syndrome) is a cardiac disorder that is inherited as an autosomal dominant trait. Affected family members suffer from recurrent syncope and sudden death due to ventricular arrhythmias. Recently, we identified a DNA marker on the short arm of chromosome 11 (the Harvey ras-1 locus [H-ras-1]) that was completely linked to the LQT locus in one large family. In the study presented here, we performed linkage investigations on six new and unrelated families with LQT. The LQT locus was again completely linked to the H-ras-1 locus in all families examined, with a combined lod score of 5.25 at a recombination fraction of 0. This work confirms our previous assignment of the LQT locus to chromosome 11p and supports the hypothesis that LQT is genetically homogeneous. As no obligate recombinants were identified in either this or our previous study, the H-ras-1 protooncogene remains a candidate for the LQT disease gene. Identification of LQT families with locus homogeneity is an important step in the development of a refined genetic map of this locus and will help determine whether the H-ras-1 marker would be of general use for presymptomatic diagnosis of this potentially fatal, but treatable, disorder.

Chromosome Mapping↗
PubMed1990

Multifiber gradient-index lens laser angioplasty probe.

A novel laser angioplasty probe fabricated with a gradient-index (GRIN) lens positioned at the tip of a seven-fiber bundle is presented. The combination of the GRIN lens and the fiberoptic bundle provides selectable optical directionality in either the axial direction or one of six off-axis directions for illumination of the arterial wall. The probe diameter (1 mm) is small enough for use in coronary laser angioplasty, and the probe is shown to transmit laser light and receive fluorescent signals simultaneously. In a 2 mm diameter lumen, the spot width in a plane normal to the axis of the lens is about 2 mm and the lateral spot size is approximately 10 mm long. The ability to direct the probe's beam pattern angularly should provide flexibility in both diagnosis and treatment.

Angioplasty, Balloon↗
PubMed1990

Thermal laser probe angioplasty: influence of constant tip temperature, plaque composition, and probe/vessel diameter ratio.

Thermal laser angioplasty uses constant laser power, producing widely variable tip temperatures in vivo. Results have been suboptimal. We studied the effect of 50-400 degrees C tip temperatures on depth of ablation at 192 sites on plaqued and normal human aorta in vitro, and the angiographic and histologic response in vivo of 300-400 degrees C at probe/vessel ratios of 0.5-1.0, in 40 normal canine femoral artery segments. In vitro, there was a direct relationship between tip temperature and depth of ablation, r = 0.71 (all segments), r = 0.74 for fibrous plaque, but a poor correlation in fatty plaque r = 0.35. In fibrous plaque, there was proportionately more ablation at tip temperatures greater than 300 degrees C, mean depth 0.62 mm, than at 150-300 degrees C, mean 0.37 mm, (P less than .001). Ablation was similar in plaqued and normal aorta. In vivo, 300 degrees C, 350 degrees C, and 400 degrees C produced similar effects. At probe/vessel ratios less than 0.8, only disruption of internal elastic lamina was observed. At ratios greater than or equal to 0.8, spasm occurred in 39% (7/18), transmural damage in 28% (5/18), and perforation in one of 18. Ablation is not selective for plaque and is highly variable in fatty plaque. Tip temperatures above 300 degrees C produce greater ablation than at lower temperatures. In clinical applications, probe/vessel rations less than or equal to 0.7 may be most appropriate, and it appears that thermal remodeling may contribute more to outcome than plaque ablation.

Angioplasty, Laser↗
PubMed1990

In vivo photosensitizer-enhanced laser angioplasty in atherosclerotic Yucatan miniswine.

Photosensitization of atherosclerotic (Ath) plaque with exogenous chromophores may confine laser irradiation (LI) injury to Ath plaque and allow safer and more efficacious laser angioplasty. Dihematoporphyrin ether (DHE) accumulates preferentially in plaque, and previous in vitro LI studies have shown confinement of LI injury to plaque. To further evaluate DHE enhanced laser angioplasty, 5 Ath Yucatan miniswine with 8 iliofemoral stenoses (Sten) were treated with 2.5 mg/kg of DHE IV. Twenty-four hours later, 632 nm continuous wave LI was delivered to Sten using 200mu core optical fiber with a 582mu x 1cm diffusing tip. Angiograms were performed before, immediately after, and two weeks following LI. 6 of 8 vessels showed improvement. Control mean Sten was 71%, immediate post LI was 55% and 2 weeks post LI was 19% Sten. In 4 of 6 responding vessels, there was 0% Sten at 2 weeks post LI and the previously stenotic segments appeared normal. 2 of 6 responders showed only modest improvement, from control mean Sten of 83% to 55% Sten at 2 weeks. 2 of 8 vessels showed no improvement. There were no perforations or dissections. The excellent results in some vessels demonstrate the potential of photosensitizer enhanced LI as very effective primary therapy of Ath. The time course of improvement indicates that both immediate thermal and delayed photochemical (photodynamic therapy) effects are operative. Further studies are required to identify reasons for failure in some vessels.

Angioplasty, Laser↗
PubMed1990

Septic arthritis in the elderly.

Twenty-one patients older than 60 years of age with septic arthritis were reviewed over a ten-year period. The knee was the joint most commonly involved. Concurrent medical illnesses were noted in the majority of patients, with diabetes mellitus present in 24%. Seventy-one percent of patients had roentgenographic evidence of preexisting joint disease in the affected joint. Most patients were afebrile and had normal white blood cell counts at the time of admission. The erythrocyte sedimentation rate was elevated in all patients tested, with an average value of 79. Despite surgical treatment in the majority of patients, the complication rate was high, with 38% developing osteomyelitis; 14%, secondary osteoarthritis; and 19%, mortality due to sepsis. Septic arthritis in the elderly is difficult to diagnose and carries a poor prognosis despite aggressive management.

Aged↗
PubMed1989

Catheter-directed neodymium:YAG laser injury of the left ventricle for arrhythmia ablation: dosimetry and hemodynamic, hematologic, and electrophysiologic effects.

The study evaluated catheter-directed laser injury of the left ventricular myocardium in a canine model as a potential method for treatment of resistant ventricular tachycardia. The relationship between laser energy delivered, the laser delivery characteristics, and the lesion size was evaluated both in vitro and in vivo. The effect of laser injury on several hematologic and hemodynamic parameters was studied. Programmed electrical stimulation studies were performed to assess the proarrhythmia potential of laser injury of the myocardium. The results showed the depth and diameter of myocardial injury to be directly related to total laser energy applied. Both depth and diameter of injury were increased by multiple applications of laser energy to the same myocardial location. One-half to full thickness left ventricular injury was produced without perforation or embolization. Endocardial vaporization occurred only with laser powers higher than necessary to produce full-thickness injury. There was no sustained effect on the hemodynamic or hematologic variables studied, nor were proarrhythmia effects identified. The laser injury produced in these studies was of smaller magnitude than might be necessary for clinical arrhythmia ablation, and the lack of sustained hemodynamic effects and pro-arrhythmia potential needs to be verified in subsequent studies with larger laser lesions. The results support continued evaluation of catheter-directed laser injury of the myocardium as a potential method for elimination of life-threatening ventricular arrhythmias.

Animals↗
PubMed1987

Laser catheter ablation of simulated ventricular tachycardia.

Catheter-directed laser injury of the left ventricular endocardium for ablation of ventricular tachycardia was studied in a canine model of simulated ventricular tachycardia. Bipolar plunge electrodes were placed at thoracotomy into the left ventricular endocardium in nine anesthetized dogs. Ventricular tachycardia was simulated by pacing at 200 beats per minute. After four days of recovery, catheter-directed neodymium:yttrium-aluminum-garnet laser injury was produced at the site of earliest recorded electrical activation during pacing tachycardia as detected by endocardial catheter mapping. Immediately after laser injury and again five days after injury, pacing tachycardia was attempted. Failure to pace after laser injury was defined as successful arrhythmia ablation. In 3/9 (33%) experiments, the laser-injured tissue surrounded the tachycardia source (pacing wires), and pacing-simulated ventricular tachycardia was prevented. When the laser injury did not involve the tachycardia source, 6/9 animals, due to limitations of the mapping system, pacing was not prevented. One animal developed sustained ventricular tachycardia during laser injury, with conversion to sinus rhythm by lidocaine. One animal, without recognized ventricular arrhythmia, died five days after laser injury. No unusual findings were noted at autopsy. These preliminary data suggest that catheter-directed laser-induced injury can ablate arrhythmia sources. Further studies are indicated in a more physiologic model, and the safety and risks of the procedure need further evaluation.

Animals↗