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Biomedical subjects

J S Gill

Publications and source records attributed to J S Gill.

At least 19 recordsLinked to original sources
PubMed1995

Free radicals irreversibly decrease Ca2+ currents in isolated guinea-pig ventricular myocytes.

The effects of free radicals on voltage-gated Ca2+ currents (ICa) were investigated in single guinea-pig ventricular myocytes using the whole-cell clamp technique. ICa was measured in the baseline state and after the application of free radicals from cumene hydroperoxide or generated from the addition of purine to xanthine oxidase. ICa decreased from 846 +/- 533 (S.D.) pA to 688 +/- 444 pA (n = 7, P < 0.05) in the presence of 100 microM cumene hydroperoxide and from 708 +/- 157 pA to 457 +/- 163 pA (n = 5, P < 0.0001) in the presence of 500 microM cumene hydroperoxide. ICa also decreased from 1303 +/- 560 pA to 965 +/- 360 pA in the presence of the free radical generating system (2.3 mM purine plus 20 U/l xanthine oxidase). The reduced ICa could not be restored by washing for up to 5 min using normal recording solution. We conclude that ICa is decreased in the presence of cumene hydroperoxide and an oxygen-derived free radical generating system in single guinea-pig ventricular myocytes. The cellular Ca2+ overload observed in free radical mediated reperfusion injury is therefore unlikely to result from an increase in sarcolemmal Ca2+ entry via voltage-gated Ca2+ channels.

Animals↗
PubMed1995

Mechanism of suramin toxicity in stable myelinating dorsal root ganglion cultures.

Suramin is an experimental chemotherapeutic agent which produces a severe dose-related neuropathy. Suramin inhibits axonal growth from rat dorsal root ganglion neurons. This inhibition is dose dependent and reversed by increasing nerve growth factor concentrations. In this study, myelinating dorsal root ganglion cultures were exposed to various concentrations of suramin and nerve growth factor. Effects were assessed with quantitative light and electron microscopy. Using a systematic sampling technique, suramin was observed to produce dose and time-dependent myelinated fiber degeneration. With 9-day exposure, there was no effect with suramin concentrations of 100 microM or less. At 200 microM, 17% of the myelinated fibers were degenerating at 4 days and 53.3% by 9 days. At 300 microM, 72.7% of the myelinated fibers and at 1316 microM, 88.7% of the myelinated fibers were degenerating at 4 days. It appeared that secondary demyelination was the major process. Large multilamellar inclusion bodies filled Schwann cells, particularly those investing unmyelinated fibers and dorsal root ganglia neuron cell bodies. The size and frequency of these inclusions increased with prolonged exposure to suramin (300 microM). Immunohistochemistry revealed that the inclusions were composed primarily of GM1 ganglioside. These effects were not influenced by increasing nerve growth factor up to 500 ng/ml. We conclude that suramin causes injury to both axons and Schwann cells that is not prevented by NGF and produces and experimental form of GM1 gangliosidosis.

Animals↗
PubMed1995

Acute changes in atrial natriuretic peptide, insulin-like growth factor-1, and lactate levels during left anterior descending coronary artery angioplasty.

This study examines acute changes in circulating levels of atrial natriuretic peptide (ANP) and insulin-like growth factor (IGF-1) during short periods of myocardial ischemia experienced at coronary angioplasty. Ten patients (mean age 55.7 +/- 3.9 years, nine men) undergoing angioplasty to the left anterior descending coronary artery were studied. Angioplasty of the left anterior descending coronary artery was performed with the balloon inflations maintained at 6 to 10 atm for 20 to 90 seconds. Blood was sampled from the coronary sinus for ANP, IGF-1 (both total and free), and lactate levels at (1) after catheterization of the coronary sinus, (2) after the initial left coronary angiography, (3) immediately after balloon deflation, and (4) 5 minutes after deflation. ANP levels (pmol/L +/- SEM) rose significantly at the end of balloon deflation (13.4 +/- 2.8; p < 0.01) compared with baseline levels (8.8 +/- 1.9). This rise was sustained for at least 5 minutes after balloon deflation (13.7 +/- 3.1; p < 0.01). ANP levels were not affected by the injections of angiographic contrast media. Free IGF-1 levels rose after injections of radiographic contrast but not after balloon inflation or deflation. Total IGF-1 levels did not change significantly at any of the sampling times. Lactic acid (mmol/L) levels rose at the end of balloon inflation (2.66 +/- 0.6) compared with baseline (2.13 +/- 0.7; p < 0.05) but returned to normal within 5 minutes of balloon deflation. Neither lactic acid levels nor release of ANP or IGF-1 correlated with the initial left ventricular end-diastolic pressure or the degree of electrocardiographic ST depression during the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗
PubMed1994

Alteration of the QT/RR relationship in patients with idiopathic ventricular tachycardia.

It has been shown that alterations in QT/RR relationship may be associated arrhythmogenesis in several clinical settings. In the present study the QT/RR relationship was studied in 20 patients with idiopathic ventricular tachycardia (12 men and 8 women, aged 41 +/- 14 years) compared to 20 normal subjects (9 men and 11 women, aged 39 +/- 13 years). All the patients were off any antiarrhythmic drugs and had no evidence of intraventricular conduction defects. The QT intervals and their preceding RR intervals were measured on electrocardiogram strips from 24-hour Holter tapes at hourly intervals. The differences in the maximum, minimum, and mean of either the QT interval or its corrected values between patients with idiopathic ventricular tachycardia and normal subjects were not statistically significant. There was a significant correlation between the QT and RR intervals in normal subjects (gamma = 0.73 +/- 0.12, P < 0.05) and in patients with idiopathic ventricular tachycardia (gamma = 0.80 +/- 0.10, P < 0.05). However, the linear regression line of the QT interval against the RR interval were significantly (P < 0.001) altered in patients with idiopathic ventricular tachycardia (QT = 0.24 +/- 0.18 RR) compared to normal subjects (QT = 0.27 +/- 0.12 RR). We conclude that although there is no significant change in the QT interval and its corrected values, the QT/RR relationship is significantly altered in patients with idiopathic ventricular tachycardia as compared to normal subjects. This may be of importance in the pathogenesis of idiopathic ventricular tachycardia in these patients.

Activities of Daily Living↗
PubMed1994

Serologic surveillance for the Lyme disease spirochete, Borrelia burgdorferi, in Minnesota by using white-tailed deer as sentinel animals.

To determine the effectiveness of white-tailed deer as sentinel animals in serologic surveillance programs for Borrelia burgdorferi, we performed enzyme-linked immunosorbent assay (ELISA) and Western immunoblotting analyses on 467 deer serum samples. The seropositivity rate in the ELISA was 5% for the 150 samples collected at the three sites in which the tick Ixodes scapularis was absent. The three sites with established I. scapularis populations had a seropositivity rate of 80% for 317 samples. Results were similar for two closely situated sites, one with an established I. scapularis population and one without; these sites were only 15 km apart. Rates of seropositivity were significantly higher in yearling and adult deer than in fawns. The mean numbers of bands seen on Western immunoblots were 3.0 for samples negative in the ELISA and 13.8 for samples positive in the ELISA; all of these samples were collected from sites in which I. scapularis was established. At sites in which I. scapularis was absent, the mean numbers of bands seen were 1.6 for samples negative in the ELISA and 8.2 for samples positive in the ELISA. There were 14 different B. burgdorferi antigens that reacted with more than 50% of the ELISA-positive samples from areas with I. scapularis. A 19.5-kDa antigen reacted with 94% of the ELISA-positive samples. Reactivity against OspA and OspB was weak a infrequent (2%). Serologic analysis of white-tailed deer sera appears to be an accurate and sensitive surveillance method for determining whether B. burgdorferi is present in specific geographic locations.

Animals↗
PubMed1994

Heart rate variability and its relation to ventricular arrhythmias in congestive heart failure.

BACKGROUND: It has been shown that heart rate variability is decreased in patients with congestive heart failure and that depressed heart rate variability is associated with a propensity to ventricular arrhythmias. Little is known, however, about heart rate variability in patients with both congestive heart failure and ventricular arrhythmias. METHODS: Spectral heart rate variability was analysed from 24 hour ambulatory electrocardiograms in 15 controls, 15 patients with non-sustained ventricular tachycardia associated with clinically normal hearts (NHVT group), and 40 patients with congestive heart failure (CHF group) secondary to either ischaemic heart disease (n = 15) or idiopathic dilated cardiomyopathy (n = 25). Of the 40 patients with congestive heart failure 15 had no appreciable ventricular arrhythmias (ventricular extrasystoles < 10 beats/h and no salvos) and formed the CHF-VA- group. Another 15 patients with congestive heart failure and non-sustained ventricular tachycardia formed the CHF-NSVT group. RESULTS: Heart rate variability was significantly lower in the CHF group than in controls (mean (SD) total frequency 23 (12) v 43 (13) ms; low frequency 12 (8) v 28 (9) ms; high frequency 8 (5) v 14 (7) ms; p < 0.001). The differences in heart rate variability between controls and the NHVT group, between ischaemic heart disease and dilated cardiomyopathy, and between the CHF-VA- and CHF-NSVT groups were not significant. In the CHF group heart rate variability was significantly related to left ventricular ejection fraction but not associated with ventricular arrhythmias. The frequency of ventricular extrasystoles was significantly related to the high frequency component of heart rate variability (r = 0.54, p < 0.05) in the NHVT group. Stepwise multiple regression analysis showed that in the CHF group, heart rate variability was predominantly related to left ventricular ejection fraction (p < 0.05). There was no significant difference in heart rate variability between survivors (n = 34) and those who died suddenly (n = 6) at one year of follow up in the CHF group. CONCLUSION: In patients with congestive heart failure, heart rate variability is significantly decreased. The depressed heart rate variability is principally related to the degree of left ventricular impairment and is independent of aetiology and the presence of ventricular arrhythmias. The data suggest that analysis of heart rate variability does not help the identification of patients with congestive heart failure at increased risk of sudden death.

Adult↗
PubMed1994

Hepatitis C.

Hepatitis C is particularly prevalent among injecting drug users. The infection is asymptomatic over 50% of the time. A significant proportion of those infected ultimately develop cirrhosis or carcinoma of the liver or both. While prevention is the best form of treatment, alpha interferon may benefit up to 30% of those with active infection.

Hepatitis C↗
PubMed1993

Blood pressure and industrial lead exposure.

The association between environmental lead exposure and raised blood pressure remains controversial. This association was examined in a cross-sectional study in 1981 on 809 male workers who were occupationally exposed to lead in a factory manufacturing car lead accumulator batteries in Birmingham, United Kingdom. Lead exposure was assessed by blood lead levels, blood zinc protoporphyrin levels, and years of industrial exposure to lead. The geometric mean blood lead level was 31.6 micrograms/dl with minimum and maximum values of 0 microgram/dl and 98 micrograms/dl, respectively. Unadjusted systolic blood pressure rose with increasing blood lead levels (analysis of variance, F = 3.3, p < 0.05) from 127 mmHg (95% confidence interval (CI) 123.5-130.5) in men with blood lead levels less than 21 micrograms/dl to 133 mmHg (95% CI 128.7-137.3) in men with levels exceeding 50 micrograms/dl. Following adjustment for the confounding effects of age, body mass index, and alcohol consumption, however, the effect of blood lead on systolic pressure was diminished (analysis of variance, F = 1.3, not significant) to 129 mmHg and 132 mmHg in the respective categories. There was no association between diastolic blood pressure and blood lead. Zinc protoporphyrin levels and years of industrial lead exposure did not raise adjusted systolic or diastolic pressure. In conclusion, subject to the limitations inherent in a cross-sectional survey, the findings are consistent with a weak effect of industrial lead exposure on systolic blood pressure, within the range of exposures observed in this study.

Adult↗
PubMed1993

Treatment of theileriosis in crossbred cattle in the Punjab.

One hundred and nine cases of bovine tropical theileriosis (Theileria annulata infection) in Punjab State, India, were treated with oxytetracycline (23 cases) or buparvaquone (86 cases). Ages of affected cattle ranged from 6 days to 3 years. Oxytetracycline cured only 7 animals (30.4%), all of them calves below 15 days old, while buparvaquone cured all but one (98.8%), a severely affected 10 day old calf. Cured cattle remained theileriosis-free for 12 to 18 months following recovery. Theileriosis in Punjab is predominantly a disease of young calves that cannot be protected by available cell-culture vaccines. It is suggested that the most economical way to control theileriosis in India would be to immunise calves by infection with sporozoite stabilate and simultaneous treatment with tetracycline, and to reserve buparvaquone for the treatment of clinical cases, in cattle of all ages.

Age Factors↗
PubMed1993

Dynamics of the QT interval in patients with exercise-induced ventricular tachycardia in normal and abnormal hearts.

Inhomogeneity of ventricular repolarization reflected in prolongation of the QT interval of the surface electrocardiogram can predispose patients to ventricular arrhythmia. This study examines whether an abnormality of QT adaptation to changes in heart rate is likely to be of importance in the pathogenesis of ventricular tachycardia (VT) in patients with and without underlying structural heart disease. The QT-R-R relationship during exercise was studied in 52 patients. Forty-two patients had VT associated with a "clinically normal" heart (idiopathic VT), of which 23 had no VT on exercise and 19 had exercise-induced VT. These patients were compared to 10 subjects with exercise-induced VT related to ischemic heart disease. The QT interval was measured manually from computer-averaged QRS complexes recorded at 1- to 3-minute intervals during treadmill exercise tests. An approximately linear association existed between the QT and R-R intervals within the range of heart rates observed. The slope of the QT-R-R relation was lower in patients with structural heart disease (0.23 +/- 0.06) than in patients with normal hearts with (0.29 +/- 0.12) and without (0.29 +/- 0.12) exercise-induced VT (p < 0.05). The intercept of the regression line was higher in patients with structurally abnormal hearts (209.2 +/- 55.3 msec) than in patients with idiopathic VT with (155.6 +/- 49.7 msec) and without (157.7 +/- 69.0 msec) exercise-induced VT (p < 0.02). The corrected QT (Bazett's formula) was similar all three groups at rest, but was higher in patients with structurally abnormal hearts at peak exercise, 449.6 +/- 28.0 versus 425.8 +/- 27.4 msec (idiopathic VT, exercise induced) versus 427.3 +/- 26.6 msec (idiopathic VT, not exercise induced) (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Verapamil for the suppression of idiopathic ventricular tachycardia of left bundle branch block-like morphology.

This study examines the efficacy of verapamil for the suppression of idiopathic ventricular tachycardia (VT) of left bundle branch block LBBB-like morphology. Forty-two patients (mean age 36.2 +/- 12.1 years; 20 men and 22 women) with VT and without any underlying cardiac abnormality on clinical examination and noninvasive investigation were studied. The inducibility of clinical VT was examined by treadmill exercise testing and programmed ventricular stimulation (PVS). In 29 patients VT was inducible by exercise testing, in 24 by PVS, and in 23 there was evidence of VT on Holter monitoring. After baseline testing, patients were treated with verapamil 120 mg thrice daily for at least 5 half-lives for the drug to load before evaluation. With Holter monitoring, 74% of patients with evidence of VT at baseline testing demonstrated a change of status from nonsustained VT to no VT or from sustained VT to nonsustained VT. Four patients had nonsustained VT during verapamil treatment but no VT at baseline. There was a significant reduction in the number of ventricular ectopic beats over 24 hours (baseline: 15,541 +/- 17,599 vs verapamil treatment: 8892 +/- 15,582, p < 0.01). Exercise-induced VT was suppressed in 56% of patients with VT during baseline testing, but no effect of verapamil on the tachycardia was observed in 26%. The remaining patients demonstrated a partial response to verapamil; the rate of VT was unchanged, although the duration of the runs was reduced. Sustained monomorphic VT was inducible in only 5 patients, of whom 4 were rendered noninducible; 1 patient remained inducible.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Heterogeneity of the human myocardial sympathetic innervation: in vivo demonstration by iodine 123-labeled meta-iodobenzylguanidine scintigraphy.

The normal pattern of the myocardial sympathetic innervation was studied in 15 subjects using single photon emission computed tomography (SPECT) gamma scintigraphy with iodine 123-labeled meta-iodobenzylguanidine (I123MIBG). Seven young subjects (mean age 29.4 +/- 7.5 years SD) with supraventricular tachycardia and eight older patients (mean age 53.0 +/- 5.1 years SD) with normal coronary arteries at cardiac catheterization and normal thallium-201 scintigrams were studied. MIBG uptake in the hearts of six patients with complete cardiac denervation after orthotopic cardiac transplantation was also studied. MIBG scintigrams were reconstructed into bull's-eye target plots and divided into eight equal sectors. Within each sector, four areas representing the apical, two midventricular, and basal regions were defined. There was a reduction in counts in the older group of subjects with normal coronary anatomy (1218.2 +/- 198.4) as compared with younger subjects with supraventricular tachycardia (1124.4 +/- 317.6), (F = 15.0, df = 1, p < 0.001). The difference was lost after adjustment for age (p = 0.2) by means of analysis of covariance. There was a difference in counts within different sectors of the scan (F = 5.7, df = 7, p < 0.001), with lateral and anterior sectors having higher counts than septal and inferior sectors. There was no difference in the counts within areas of the scan (F = 0.04, df = 3, not significant [NS]) or different areas within the sectors (F = 1.1, df = 21, NS). A small diminution of counts (approximately 10%) in the 10 o'clock region of the bull's-eye target plot was observed in some scans.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Iodobenzylguanidine↗
PubMed1993

Effects of propafenone on calcium currents in single ventricular myocytes of guinea-pig.

1. The effects of propafenone on the inward calcium current (ICa) were investigated in isolated single ventricular myocytes of the guinea-pig by the whole-cell clamp method. Propafenone inhibited ICa in a dose-dependent manner at concentrations of propafenone ranging from 1 x 10(-8) to 1 x 10(-3) M and half maximal block of ICa occurred at a propafenone concentration of 1.5 x 10(-6) M. Propafenone did not change the current-voltage relation of ICa other than a reduction in amplitude and showed no clear use- or frequency-dependent effects upon ICa (stimulation frequencies from 0.03 to 2 Hz). Propafenone did not alter the steady-state inactivation process: the half maximal activation potentials were 18.5 +/- 2.2 mV in the control state and 20.9 +/- 5.0 mV in the presence of 1 x 10(-6) M propafenone (n = 12, NS). Propafenone (1 x 10(-6) M) increased the half-time of reactivation by 73.9% (n = 6, 212.3 +/- 1.2 ms vs 369.2 +/- 1.5 ms, P < 0.05). 2. We conclude that propafenone blocks ICa in a concentration-dependent and a channel state-, use- or frequency-independent manner. The ICa blockade elicited by propafenone at clinically therapeutic plasma concentration is significant and may be involved in its anti-arrhythmic effects.

Animals↗
PubMed1993

Serologic analysis of white-tailed deer sera for antibodies to Borrelia burgdorferi by enzyme-linked immunosorbent assay and western immunoblotting.

White-tailed deer serum samples were collected in the Minneapolis-St. Paul, Minn., metropolitan area during the fall and winter months from 1989 to 1992 and analyzed for antibodies to Borrelia burgdorferi, the etiologic agent of Lyme borreliosis. Ninety-eight percent of the serum samples were collected from regions where currently the vector tick, Ixodes dammini, is nonexistent. Antibodies to B. burgdorferi were detected in 2.2% of 508 samples by enzyme-linked immunosorbent assay, and their presence was confirmed by Western immunoblot analysis. Western immunoblotting yielded mean numbers of reactive bands of 0.1 and 6.0 for samples that were negative and positive for antibodies by enzyme-linked immunosorbent assay, respectively. The molecular weights of the antigens in many of the reactive bands from positive samples were similar to the molecular weights of antigens reactive with samples from humans with Lyme borreliosis. An antibody response to the major outer surface proteins A and B was not detected. Serologic analysis of deer sera may provide a valuable method for surveillance programs designed to monitor the spread of B. burgdorferi in nature.

Animals↗
PubMed1993

Asymmetry of cardiac [123I] meta-iodobenzyl-guanidine scans in patients with ventricular tachycardia and a "clinically normal" heart.

OBJECTIVE: Patients with exercise induced ventricular tachycardia associated with a "clinically normal" heart may have an abnormality of the regional distribution of the cardiac sympathetic nerve supply. In this study the regional distribution of the myocardial nerve supply in patients with ventricular tachycardia (VT) and control subjects was examined by [123] meta-iodobenzylguanidine (MIBG) scanning. PATIENTS AND DESIGN: Eight patients with exercise induced VT and seven patients with VT unrelated to exercise with "clinically normal" hearts were studied and compared with a control group of six subjects with atrioventricular reentrant tachycardia not related to exercise and eight patients with angiographically normal left ventricular function and normal coronary anatomy who had thallium scans without evidence of ischaemia or fixed perfusion deficits. METHODS: Single photon emission computed tomography gamma scanning was performed in patients three hours after intravenous injection of MIBG. The left ventricular MIBG uptake data was processed into bull's-eye target plots. The inferior portion of the scan frequently showed artefact due to uptake of MIBG in the liver or spleen and was not used for statistical analysis. Asymmetry of uptake was defined as a ratio of uptake exceeding 1.25 in the upper quadrants (posterior (anterolateral free wall)/anterior (anteroseptal region)) of the MIBG scan. RESULTS: Patients with VT had a higher proportion of asymmetrical MIBG scans (47%) than subjects in the control groups (0%) and this was particularly obvious in the patients with exercise induced VT (62.5%). This suggests that patients with VT may have relative denervation in the septal portion of the left ventricle leading to an imbalance of the sympathetic supply to the myocardium and locally imbalanced sympathetic or parasympathetic interactions. Considerable evidence from animal experiments suggests that imbalance of the sympathetic supply to the myocardium is important in the genesis of ventricular arrhythmia. CONCLUSIONS: These results support the hypothesis that selective denervation of the human myocardium may be an important mechanism in the genesis of VT in "clinically normal" hearts.

3-Iodobenzylguanidine↗
PubMed1993

Abnormal autonomic modulation of QT interval in patients with idiopathic ventricular tachycardia associated with clinically normal hearts.

BACKGROUND: Idiopathic ventricular tachycardia (VT) occurs in a small but important subset of patients without clinically overt heart disease. The mechanism of the arrhythmogenesis remains unclear in these patients. This study examines modulation of the QT interval by the autonomic nervous system in a group of patients with idiopathic ventricular tachycardia. METHODS: Cardiac autonomic activity and ventricular repolarisation were studied in 27 patients with VT associated with a clinically normal heart (NHVT) and in 20 normal subjects. All the patients were in sinus rhythm, had normal atrioventricular conduction, and were in a drug free state. Cardiac efferent autonomic activity was measured by spectral analysis of heart rate variability from 24 hour ambulatory electrocardiograms on a Holter analysis system (Marquette). Ventricular repolarisation was evaluated by measuring the QT intervals from the same 24 hour Holter tapes at one hour intervals. RESULTS: There was no difference in any of the QT interval variables including the maximum, minimum, and mean of both the QT interval and its corrected value (Bazett's formula) between patients with NHVT and normal subjects. The high frequency component (0.04-0.15 Hz) of heart rate variability was significantly decreased in patients with NHVT compared with normal subjects (16 (8) v 21 (12) ms, p < 0.05). There was a significant correlation between the spectral variables of heart rate variability and the mean, maximal, and minimal QT intervals in normal subjects, whereas the relation was lost in patients with NHVT. No difference was found in mean heart rate between normal subjects and patients with NHVT (70 (9) v 72 (13) beats/min, NS). CONCLUSIONS: The high frequency component of heart rate variability is significantly decreased and the relation of QT interval to heart rate variability is significantly altered in patients with NHVT as compared with normal subjects. These findings suggest that abnormal modulation of the QT interval by the autonomic nervous system may play an important part in the arrhythmogenesis of NHVT. This might result from impaired vagal efferent cardiac activity in these patients.

Adolescent↗