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Biomedical subjects

M Talbot

Publications and source records attributed to M Talbot.

At least 19 recordsLinked to original sources
PubMed2000

Left ventricular or biventricular pacing improves cardiac function at diminished energy cost in patients with dilated cardiomyopathy and left bundle-branch block.

BACKGROUND: Left ventricular or biventricular pacing/stimulation can acutely improve systolic function in patients with dilated cardiomyopathy (DCM) and intraventricular conduction delay by resynchronizing contraction. Most heart failure therapies directly enhancing systolic function do so while concomitantly increasing myocardial oxygen consumption (MVO(2)). We hypothesized that pacing/stimulation, in contrast, incurs systolic benefits without raising energy demand. METHODS AND RESULTS: Ten DCM patients with left bundle-branch block (ejection fraction 20+/-3%, QRS duration 179+/-3 ms, mean+/-SEM) underwent cardiac catheterization to measure ventricular and aortic pressure, coronary blood flow, arterial-coronary sinus oxygen difference (DeltaAVO(2)), and MVO(2). Data were measured under sinus rhythm or with left ventricular or biventricular pacing/stimulation at the same heart rate. These results were then contrasted to intravenous dobutamine (n=7) titrated to match systolic changes during LV pacing. Systolic function rose quickly and substantially from LV pacing (18+/-4% rise in arterial pulse pressure, which correlates with cardiac output, and 43+/-6% increase in dP/dt(max); both P<0.01). However, DeltaAVO(2) and MVO(2) declined -4+/-2% and -8+/-6.5%, respectively (both P<0.05). Similar results were obtained with biventricular activation. In contrast, dobutamine raised dP/dt(max) 37+/-6%, accompanied by a 22+/-11% rise in per-beat MVO(2) (P<0.05 versus pacing). CONCLUSIONS: Ventricular resynchronization by left ventricular or biventricular pacing/stimulation in DCM patients with left bundle-branch block acutely enhances systolic function while modestly lowering energy cost. This should prove valuable for treating DCM patients with basal dyssynchrony.

Bundle-Branch Block↗
PubMed2000

The design and synthesis of thrombin inhibitors: the introduction of in vivo efficacy and oral bioavailability into benzthiazolylalanine inhibitors.

The further optimisation of the novel lead compound CGH752 (Fig. 1) is described. By introducing various substituents into the 6-position of the 3,3-dimethyltetrahydroquinoline (DMTHQS) ring we have been able to favourably affect the in vitro and in vivo activity, and the pharmacokinetics of such compounds. One of the inhibitors synthesised (CGH1484) is bioavailable and shows efficacy in animal models of thrombosis.

Administration, Oral↗
PubMed2000

Predictors of systolic augmentation from left ventricular preexcitation in patients with dilated cardiomyopathy and intraventricular conduction delay.

BACKGROUND: VDD pacing can enhance systolic function in patients with dilated cardiomyopathy and discoordinate contraction; however, identification of patients likely to benefit is unclear. We tested predictors of systolic responsiveness on the basis of global parameters as well as directly assessed mechanical dyssynchrony. METHODS AND RESULTS: Twenty-two DCM patients with conduction delay were studied by cardiac catheterization with a dual-sensor micromanometer to measure LV and aortic pressures during sinus rhythm and LV free-wall pacing. Pacing enhanced isovolumetric (dP/dt(max)) and ejection-phase (pulse pressure, PP) systolic function by 35+/-21% and 16.4+/-11%, respectively, and these changes correlated directly (r=0.7, P=0.001). %DeltadP/dt(max) was weakly predicted by baseline QRS (r=0.6, P<0.02), more strongly by baseline dP/dt(max) (r=0.7, P=0.001), and best by bidiscriminate analysis combining baseline dP/dt(max) < or =700 mm Hg/s and QRS > or =155 ms to predict %DeltadP/dt(max) > or =25% and %DeltaPP > or =10% (P<0.0005, chi(2)), with no false-positives. Benefit could not be predicted by %DeltaQRS. To test whether basal mechanical dyssynchrony predicted responsiveness to LV pacing, circumferential strains were determined at approximately 80 sites throughout the LV by tagged MRI in 8 DCM patients and 7 additional control subjects. Strain variance at time of maximal shortening indexed dyssynchrony, averaging 28.0+/-7.1% in normal subjects versus 201.4+/-84.3% in DCM patients (P=0.001). Mechanical dyssynchrony also correlated directly with %DeltadP/dt(max) (r=0.85, P=0.008). Conclusions-These results show that although mechanical dyssynchrony is a key predictor for pacing efficacy in DCM patients with conduction delay, combining information about QRS and basal dP/dt(max) provides an excellent tool to identify maximal responders.

Adult↗
PubMed2000

Two consecutive pregnancies during inadvertent gonadotropin-releasing hormone agonist desensitization.

OBJECTIVE: To describe two consecutive spontaneous pregnancies during luteal-phase down-regulation with a GnRH-a. DESIGN: Case report. SETTING: University-affiliated reproductive medicine unit. PATIENT(S): A 33-year-old woman with a history of failed uterine tubal reanastomosis. INTERVENTION(S): Four IVF cycles. MAIN OUTCOME MEASURE(S): Pregnancy. RESULT(S): The patient had two spontaneous pregnancies during luteal-phase down-regulation. CONCLUSION(S): Although midluteal administration of GnRH-a is not established as a treatment, there might be a beneficial effect on the endometrium via the medication's evoked gonadotropin flare.

Adult↗
PubMed2000

Secondary fractures of Le Fort I osteotomy.

PURPOSE: To report the ophthalmic complications of Le Fort I osteotomy for the correction of dentofacial deformities and to determine the maximal compressive loads applied during pterygomaxillary separation in a cadaver model. METHODS: Two cases of ophthalmic complications arising after Le Fort I osteotomy are reported. Le Fort I osteotomy was performed on five cadavers. The maximal compressive load applied during pterygomaxillary separation was recorded with a 10 kN (3,000 lbf) load cell of a MTS Mini-Bionix servo-hydraulic machine (MTS, Eden Prairie, MN, U.S.A.). A paired t test was used to compare forces applied to the right and left sides. Computed tomography scans of each specimen were obtained after Le Fort I osteotomy to document secondary fractures. The skulls were subsequently stained with 1% fuschin red to highlight secondary fractures. RESULTS: Maximum compressive loads during pterygomaxillary separation ranged from 22 N (5.0 lbf) to 162 N (36.5 lbf), with an average of 106 N (23.8 lbf) (SD 47.6 N [10.7 lbf]). Forces applied on the first operative side were significantly greater than forces applied on the second operative side (p = 0.0034). Secondary fractures were found in three specimens by computed tomography and in two specimens by 1% fuschin red. All secondary fractures occurred on the second operative side. CONCLUSION: Secondary fractures in the Le Fort I osteotomy procedures occurred on the side opposite the greater maximal compressive load and on the second operative side.

Adult↗
PubMed2000

Short course oral prednisolone therapy in chronic abacterial prostatitis and prostatodynia: case reports of three responders and one non-responder.

OBJECTIVE: To report on a small group of patients with chronic abacterial prostatitis/chronic pelvic pain syndrome treated with oral corticosteroids in order to suggest a hypothesis for a future randomised controlled trial. DESIGN: A retrospective, observational report. RESULTS: Three out of the four patients reported improvement in symptoms following steroid treatment. CONCLUSIONS: These reports suggest that there is scope for conducting a randomised, placebo controlled study to investigate the role of oral corticosteroids in patients with chronic abacterial prostatitis/chronic pelvic pain syndrome who have failed on conventional therapy.

Adult↗
PubMed2000

Impaired in vivo stimulation of lipolysis in adipose tissue by selective beta2-adrenergic agonist in obese adolescent girls.

Studies performed in adults with long-standing obesity suggest a reduced lipolytic sensitivity to catecholamines in subcutaneous abdominal adipose tissue (AT). We used microdialysis to study the in situ lipolytic effects of dobutamine (selective beta1-agonist) and terbutaline (selective beta2-agonist) on glycerol release (lipolytic index) in abdominal subcutaneous AT in 10 obese girls aged 13-17 years, BMI 38 +/- 2.1 kg/m2, and in 7 lean girls aged 11-17 years, BMI 21 +/- 1.1 kg/m2, and compared them with 10 obese women aged 21-39 years, BMI 36 +/- 1.6 kg/m2, and 10 lean women aged 18-42 years, BMI 21 +/- 0.4 kg/m2. Terbutaline at 10(-6) mol/l stimulated glycerol release more efficiently in lean girls than in obese girls (peak response approximately 350 vs. 150% of control, P < 0.01). At the lower concentration of agonist, no significant difference was seen. In women, terbutaline was more effective in lean than in obese women in stimulating glycerol release at both 10(-8) mol/l (peak response lean approximately 175% vs. obese 125% of control) and 10(-6) mol/l (approximately 300 vs. 150% of control, P < 0.05). No significant difference in glycerol release between obese and lean girls or women was detected with selective beta1-stimulation. Our data demonstrate a specific impairment in the capacity of beta2-adrenergic agonists to promote lipolysis in subcutaneous abdominal adipose tissue of obese adolescent girls and women. Thus, decreased mobilization of fat during activation of the adrenergic system might be present early in the development of adolescent obesity.

Abdomen↗
PubMed1999

Optimisation of the P2 pharmacophore in a series of thrombin inhibitors: ion-dipole interactions with lysine 60G.

The optimisation of the P2 pharmacophore in a series of thrombin inhibitors is described. The interaction of a number of piperidine P2 functionalities with lysine 60G of thrombin is explored with reference to the crystal structure of inhibitor enzyme complexes. A primary ion-dipole interaction between the terminal P2 side chain group and lysine 60G is evoked to explain the SAR in this series.

Crystallography, X-Ray↗
PubMed1999

Improved left ventricular mechanics from acute VDD pacing in patients with dilated cardiomyopathy and ventricular conduction delay.

BACKGROUND: Ventricular pacing can improve hemodynamics in heart failure patients, but direct effects on left ventricular (LV) function from varying pacing site and atrioventricular (AV) delay remain unknown. We hypothesized that the magnitude and location of basal intraventricular conduction delay critically influences pacing responses and that single-site pacing in the delay-activated region yields similar or better responses to biventricular pacing. METHODS AND RESULTS: Aortic and LV pressures were measured in 18 heart failure patients (mean+/-SD: LV ejection fraction, 19+/-7%; LV end-diastolic pressure, 25+/-8 mm Hg; QRS duration, 157+/-36 ms). Data under normal sinus rhythm were compared with ventricular pacing (VDD) at varying sites and AV delays (randomized order). Right ventricular (RV) apical or midseptal pacing had negligible contractile/systolic effects. However, LV free-wall pacing raised dP/dtmax by 23.7+/-19.0% and pulse-pressure by 18.0+/-18.4% (P<0.01). Biventricular pacing yielded less change (+12.8+/-9.3% in dP/dtmax, P<0.05 versus LV). Pressure-volume analysis performed in 11 patients consistently revealed minimal changes with RV pacing but increased stroke work and lower end-systolic volumes with LV pacing. Optimal AV intervals averaged 125+/-49 ms, and within this range, AV delay had less influence on LV function than pacing site. Basal QRS duration positively correlated with %DeltadP/dtmax (P<0.005), but pacing efficacy was not associated with QRS narrowing. Conduction delay pattern generally predicted pacing sites with most effect. CONCLUSIONS: VDD pacing acutely enhances contractile function in heart failure patients with intraventricular conduction delay. Single-site pacing at the site of greatest delay achieves similar or greater benefits to biventricular pacing in such patients. These data clarify pacing-effect mechanisms and should help in candidate identification for future studies.

Adult↗
PubMed1999

Control of apoptosis in Epstein Barr virus-positive nasopharyngeal carcinoma cells: opposite effects of CD95 and CD40 stimulation.

The expression and function of CD95 and CD40 were investigated in malignant cells from EBV-positive undifferentiated nasopharyngeal carcinomas (NPCs). Large amounts of CD95 and CD40 expression were detected in 15 of 16 EBV-positive NPC specimens. In contrast, CD95 was not detected in two biopsies from patients with EBV-negative differentiated NPCs. We tested whether the CD95 apoptotic pathway was functional in NPC cells by treating two EBV-positive NPC tumor lines in vitro with a CD95 agonist. In both cases, NPC cells were extremely susceptible to CD95-mediated apoptosis, despite strong constitutive expression of Bcl-x. Combined CD40 and CD95 stimulation was used to investigate the possible anti-apoptotic activity mediated by CD40. The CD40 receptor was activated by incubating NPC cells with murine L cells producing CD154, the CD40 ligand. This treatment resulted in a strong inhibition of CD95-related cytotoxicity. Such an anti-apoptotic effect of CD40 is well known for B lymphocytes, but has not previously been reported for epithelial cells. These data suggest that NPC tumor-infiltrating lymphocytes, which often produce the CD40 ligand in situ, may increase the survival of malignant cells, thereby enhancing tumor growth in patients.

Adolescent↗
PubMed1999

Verapamil acutely reduces ventricular-vascular stiffening and improves aerobic exercise performance in elderly individuals.

OBJECTIVES: We tested the hypothesis that acute intravenous verapamil acutely enhances aerobic exercise performance in healthy older individuals in association with a combined reduction of ventricular systolic and arterial vascular stiffnesses. BACKGROUND: Age-related vascular stiffening coupled with systolic ventricular stiffening may limit cardiovascular reserve and, thus, exercise performance in aged individuals. METHODS: Nineteen healthy volunteers with mean age 70 +/- 10 years underwent maximal-effort upright ergometry tests on two separate days after receiving either 0.15 mg/kg i.v. verapamil or 0.5 N saline in a double-blind, randomized, crossover study. RESULTS: Baseline vascular stiffness, indexed by arterial pulse-wave velocity (Doppler) and augmentation index (carotid tonometry) declined with verapamil (-5.9 +/- 2.1% and -31.7 +/- 12.8%, respectively, both p < 0.05). Preload-adjusted maximal ventricular power, a surrogate for ventricular end-systolic stiffness, also declined by -9.5 +/- 3.6%. Peripheral resistance and peak filling rate were unchanged. With verapamil, exercise duration prior to the anaerobic threshold (AT) increased by nearly 50% (260 +/- 129 to 387 +/- 176 s) with a corresponding 13.4 +/- 4.7% rise in oxygen consumption (VO2) at that time (both p < 0.01). Total exercise duration prolonged by +6 +/- 2.7% (p < 0.05) with no change in maximal VO2. Baseline cardiodepression from verapamil reversed by peak exercise with net increases in stroke volume and cardiac output (p < 0.05). CONCLUSIONS: Acute intravenous verapamil reduces ventriculovascular stiffening and improves aerobic exercise performance in healthy aged individuals. This highlights a role for heart-arterial coupling in modulating exertional capacity in the elderly, suggesting a potentially therapeutic target for aged individuals with exertional limitations.

Aged↗