Biomedical subjects
Publications and source records attributed to R Grove.
We describe a biventricular stimulation mode to pace both ventricles with a single electrical stimulus between the tip of the left ventricular electrode and the tip of the right ventricular electrode: one ventricle is stimulated cathodal the other anodal.
Cardiac resynchronization therapy by multisite biventricular pacing presents an additive therapeutic option in the treatment of severe heart failure. Biventricular pacemaker implantation is challenging in patients with persistent left superior vena cava. We describe in this case report the implantation of a biventricular pacemaker using a left-sided approach in a patient with persistent left superior vena cava.
The following report illustrates the case of a 40-year old patient, who was transferred to our hospital because of a symptomatic sustained ventricular tachycardia (VT). The documented VT showed typical left bundle branch block morphology with an inferior axis, which was accompanied by repolarization abnormalities in the right precordial leads, as revealed by the surface ECG. While coronary angiography allowed the exclusion of an obstructive coronary heart disease and confirmed an intact left ventricular function, the right ventricular angiography as well as the MRI demonstrated not only reduced right ventricular function but also regional abnormalities of contraction in the inferior and diaphragmal regions and typical "outpouchings" and "bulgings". The MRI also provided evidence for sporadic fatty infiltrations of the right ventricle. In the electrophysiological study, sustained VT could be reproducibly induced, while showing the typical RVOT configuration, which corresponded to the clinically apparent VT. Since these examination results matched with the criteria of McKenna et al., arrhythmogenic right ventricular cardiomyopathy was diagnosed. The patient underwent implantation of a cardioverter-defibrillator (ICD) and medical treatment with metoprolol. This particular case report was selected because it shows a typical presentation of an ARVC. Furthermore, the present example offers the possibility of demonstrating that in the case of an ARVC in the regions of the right ventricle, arrhythmogenic areals can also be found which seem morphologically inconspicuous.
Use of maximal aerobic power (VO2(max)) testing, which requires subjects to exercise to physiological limits, may deter eligible candidates from volunteering for trials and may also be contraindicated in patients suffering from various medical illnesses. An alternative to maximal testing is submaximal testing. The Aerobic Power Index, which represents the aerobic component of the Tri-level Fitness Profile, is a submaximal test that has been shown to be reliable in trained athletes. The purpose of this study was to establish reliability of the Aerobic Power Index, as well as associated variables of VO2 (ml x kg(-1) x min(-1) and rate of perceived exertion (RPE), in a group of sedentary subjects. Results for the 20 subjects who participated in a test-retest trial indicated high reliability (ICC r = 0.98, %TEM 3.87 W x kg(-1); SEM 0.04 W x kg(-1) for the main measurement outcome of Watts per kilogram (W x kg(-1)). Oxygen uptake (ml x kg(-1)min(-1)) also demonstrated high reliability (ICC r = 0.92; %TEM 4.63 ml x kg(-1) x min(-1); SEM 0.58 ml x kg(-1) min (-1), as did RPE (ICC r = 0.97,%TEM 7.78; SEM 0.63). Limits of agreement were -0.02+/-0.16 W x kg(-1). -0.41+/-2.31 ml x kg(-1) x min(-1) for VO2 and -0.05 < or = 2.10 for RPE. These results indicate that the Aerobic Power Index is a reliable submaximal exercise test for use in sedentary subjects.
BACKGROUND: Chronic infections have been proposed to play a role in the aetiology or progression of atherosclerotic plaques. Increased risk of coronary artery disease has been suggested in patients seropositive for Helicobacter pylori. AIM: To analyse coronary specimens in patients with severe (coronary artery disease) for Helicobacter pylori specific DNA. PATIENTS AND METHODS: Atherosclerotic plaques were obtained in 46 consecutive patients (9 female, 37 male, mean age 62.7+/-9.17 years) during coronary bypass procedures. Serum was analysed for IgG -/cagA-antibodies specific for Helicobacter pylori. Polymerase chain reaction and sequence analysis were used to identify bacterial DNA. Coronary artery biopsies from 19 autopsies without coronary artery disease were examined as a control group. RESULTS: Of the 46 coronary artery disease patients, 32 (69.6%) were Helicobacter pylori seropositive. Positive results for Helicobacter pylori DNA showed 18 seropositive and 4 seronegative (with anamnesis of eradication therapy). A total of 22 patients (47.8%) of the coronary artery disease group but none of controls revealed positive DNA. In the coronary artery disease group, a correlation between DNA presence and prior myocardial infarction (p=0.008) and unstable angina (p<0.001) was found. CONCLUSION: Identification of DNA in atherosclerotic plaques of patients with severe coronary artery disease supports the hypothesis that Helicobacter pylori infection may influence the development of atherosclerosis. Our results may indicate an direct involvement of Helicobacter pylori in the progression and instability of plaques in these patients.
For 25 years, cardiac catheters have been prepared for reuse in a hospital for heart and vessel diseases, in the beginning by the hospital itself, later on by a specialized company with a standardize, validated certified procedure. Experiences with almost 100,000 interventions with flow directed catheters, diagnostic left-heart- and angiography-catheters, balloon- and electrophysiology-catheters, which were performed with reused material in more than half of these cases, are reported. All patients were informed that disposable catheters were reused. Neither the duration of the intervention, the x-ray load for the patient, the consumption of contrast media and the change rate of catheters, nor the catheter dependent complication rates were increased for reused catheters in comparison to single use. Therefore the reuse of cardiac catheters does not affect patients' safety, but is a cost-saving strategy.
BACKGROUND: Gastric infection caused by Helicobacter pylori has recently been associated with increased risk of coronary artery disease. AIM: To: 1) determine seroprevalence of Helicobacter pylori and its cytotoxin associated gene A in patients with/without coronary artery disease (group A), 2) assess influence of Helicobacter pylori eradication on coronary artery lumen reduction after percutaneous coronary angioplasty (group B) and 3) determine influence of Helicobacter pylori eradication on plasma cytokines, lipids and coagulation factors in patients subjected to percutaneous coronary angioplasty (group B). PATIENTS AND METHODS: Group A included 100 patients with coronary artery disease (subgroup 1) and 100 patients without (subgroup II). For Helicobacter pylori seroprevalence, plasma anti-Helicobacter pylori and anti-cytotoxin associated gene A IgG were examined. Group B included 40 patients with significant single-vessel coronary arterial disease and Helicobacter pylori infection confirmed by 13C-urea breath test and serologically using anti-Helicobacter pylori and anti-cytotoxin associated gene A IgG. Six months after percutaneous coronary angioplasty and triple anti-Helicobacter pylori therapy, the Helicobacter pylori status reassessed by urea breath test was negative in all but two patients of subgroup I subjected to Helicobacter pylori therapy. Coronary angiography and laboratory tests were repeated in both subgroups of group B included in the trial and reduction in coronary artery lumen in these subgroups was compared to baseline after percutaneous coronary angioplasty considered as 100%. RESULTS: Helicobacter pylori seropositivity reached 81.5% of coronary artery disease (subgroup I) and was significantly higher than that in controls without coronary artery disease (subgroup II) (51%), the odds ratio being 4.3 for Helicobacter pylori in coronary artery disease. Cytotoxin associated gene A IgG detection was also significantly higher (47.3%) in coronary artery disease than in controls (28%) giving the odds ratio about 2.3. Mean coronary artery lumen reduction in patients undergoing percutaneous coronary angioplasty + Helicobacter pylori eradication therapy (subgroup I) was significantly (p<0.05) smaller compared to percutaneous coronary angioplasty + placebo-treated subgroup II (22% vs 41%). CONCLUSIONS: 1) There is a significant link between coronary artery disease and infection with Helicobacter pylori, especially expressing CagA proteins, 2) Helicobacter pylori eradication significantly attenuates reduction in coronary artery lumen in coronary artery disease patients after percutaneous coronary angioplasty possibly by elimination of chronic inflammation and decline in proinflammatory cytokine release, and 3) Infection of Chlamydia pneumoniae in these percutaneous coronary angioplasty patients is not affected by eradication therapy.
Atrial fibrillation is due to complications a frequent clinical problem. Internal cardioversion shows a high effectiveness with conversion rates from up to 85%. Aim of this study was to evaluate the influence of body weight (body-mass-index [BMI]) on the effectiveness of different cardioversion procedures.
INTRODUCTION: The therapeutical limits of drug and surgical therapy for severe chronic heart failure make the research for adjunctive treatment options necessary. After the positive effects of AV-synchronous pacemaker stimulation in patients with dilatative cardiomyopathy and 1st degree AV-block, this study was to evaluate the benefit of transient pacemaker stimulation in patients with dilated cardiomyopathy and left bundle branch block. METHODS AND PATIENTS: 19 patients (14 male, 5 female, age 60 +/- 8 yrs) were included in the study. Inclusion criteria were congestive heart failure, stage NYHA III or greater and left bundle branch block. Transient stimulation of the myocardium was applied via two electrodes (right atrium and right ventricle) in VDD mode, whereby a series of AV-delay-times between 80 and 180 ms was tested. Thermodilution was used to determine cardiac output, pulmonary capillary pressure and pulmonary arterial pressure. RESULTS: In 16 patients, pacemaker stimulation led to a significant increase of cardiac output (3.8 +/- 0.5 l/min to 4.6 +/- 0.5 l/min; p < 0.002), cardiac index (1.90 +/- 0.20 l/min/m2 to 2.3 +/- 0.2 l/min/m2; p < 0.002) and of stroke volume (51 +/- 8 ml to 62 +/- 6 ml; p < 0.002) as well as a significant reduction of mean pulmonary capillary pressure (19 +/- 1 mmHg to 15 +/- 1 mmHg; p < 0.01). The mean pulmonary arterial pressure remained unchanged. Three patients did not benefit from the treatment. CONCLUSION: AV-sequential pacemaker-stimulation (right ventricular electrode placement) can be a valuable adjunctive therapy in selected patients with late stage congestive heart failure and left bundle branch block.
PURPOSE: This preclinical rat pilot study quantifies retinal microvessel, endothelial, and pericyte population changes produced by proton irradiation METHODS AND MATERIALS: The left eyes of rats were irradiated with single doses of 8, 14, 20, and 28 Gy protons; right eyes, with two fractions. Animals were euthanized, and eyes were removed; elastase digests were prepared, and cell populations were counted in sample fields. Results were compared with unirradiated controls. RESULTS: Progressive time- and dose-dependent endothelial cell loss occurred following all schedules. Cell loss was significantly different from control values (p < 0.001) following 28 Gy and following 20 Gy (p < 0.05) in a single dose. Endothelial cell loss was the same for single- and split-dose schedules. Progressive endothelial cell loss produced vessel collapse and acellular vessel strands. Endothelial cells were in the G(0) phase of the mitotic cycle. 28 Gy produced photoreceptor cell loss. CONCLUSION: The retinal digest is an elegant bioassay to quantify the microvessel population response. Single- and split-dose schedules appear to yield similar outcomes, in terms of endothelial cell density.
PURPOSE: The purpose of this study was to test the efficacy of a new cationic lipid formulation coupled with the cDNA encoding for the 165-residue form of vascular endothelial growth factor (VEGF(165)) to induce neovascularization and enhance blood flow in the rabbit ischemic hindlimb model. METHODS: Two days after removal of their right femoral arteries, rabbits received intramuscular injections of different concentrations of VEGF(165) or saline solution in the ischemic thigh. Tissue perfusion and increased neovascularization of the ischemic limb were assessed weekly on the basis of the calf blood pressure ratio for the ischemic/nonischemic limbs, regional blood flow to the skeletal muscles as measured with radioactive microspheres, postmortem angiography, and histology. RESULTS: At weeks 1 and 2 after surgery, animals treated with 1000 microgram of VEGF(165) had a 1.5-fold increase and a 2.5-fold increase, respectively, in the regional blood flow to both the adductor and gastrocnemius muscles of the ischemic limb. The blood pressure ratio was also greater in the treated animals than in the controls at weeks 2 and 3 after surgery. Early neovascularization in the VEGF(165) group was further documented at week 1 after surgery by more angiographically recognizable collateral vessels (angioscores were 64.13 +/- 2.51 and 38.28 +/- 3.82 for VEGF(165) and saline solution, respectively; P <.001) and by a threefold increase in the number of capillaries (vascular density) relative to the controls (P <.005). CONCLUSIONS: Intramuscular administration of a single dose of plasmid-liposomes encoding for VEGF(165) accelerates angiogenesis and increases blood flow in the rabbit hindlimb ischemic model. Therefore, this nonviral vector could be recommended for further testing for use in therapeutic angiogenesis.
BACKGROUND AND OBJECTIVE: Because there are limits to the drug treatment or surgical intervention of advanced heart failure, alternative methods are being explored. It was the aim of this study to investigate the extent to which optimal atrioventricular (AV) sequence of dual pacemaker stimulation in patients with advanced dilated cardiomyopathy (DCM) of different aetiology increases their usually much reduced cardiac output. PATIENTS AND METHODS: The study group consisted of 22 patients (five women, 17 men; aged 54-84 years) with heart failure in class I-IV (New York Heart Association classification). Temporary dual electrode stimulations (in the right atrium and ventricle) in the VDD or DDD mode were performed with programmed AV intervals between 80 and 180 ms. Cardiac output (CO), pulmonary capillary and pulmonary arterial pressures were measured via an indwelling catheter. RESULTS: In 17 patients with a 1 degree AV block and/or left bundle branch block in the surface ECG pacing produced a significant increase in CO (from 3.7 +/- 0.75 to 4.6 +/- 0.65 l/min; P < 0.005) and cardiac index (from 2.05 +/- 0.43 to 2.47 +/- 0.37 l/min/m2; P < 0.005). There was no increase in patients with normal PR interval and QRS duration. Mean pulmonary capillary and pulmonary arterial pressures remained unchanged. CONCLUSION: Alteration of AV sequence by pacemaker in selected patients in the late stage of heart failure, particularly if there is also abnormal atrioventricular and/or intraventricular conduction delay, may be an effective complementary method of treatment.
An assay measuring RNA expression levels of a gene-encoded therapeutic must distinguish between endogenous mRNA and mRNA transcribed from the transgene. Specificity for the delivered transgene is especially critical when the treatment involves genes that are expressed in the target tissue. To facilitate uniform detection of transgene RNA without interference from endogenous mRNA, we have engineered expression vectors that include a 5' untranslated region (5' UTR) containing a synthetic intron (PGL3). The synthetic intron splice junction was the target sequence for a quantitative reverse transcription (RT)-PCR assay utilizing Taq-Man technology. In this study, we demonstrate that a quantitative RT-PCR assay designed to recognize an engineered intron splice site in the 5'UTR of expression constructs effectively measures the expression level of in vivo-delivered gene therapeutics.
We report the first successful isolation and initial characterization of S-adenosylmethionine decarboxylase (SAMDC)-overexpressing cells using a transfection approach. Stably transfected MCF-7 breast cancer overproducing SAMDC (approximately 5-fold) manifested reduced ornithine decarboxylase while levels of N'-spermidine/spermine acetyltransferase were variably increased. Analysis of cellular polyamine profile showed that spermine was selectively increased (approximately 80%), while spermidine and putrescine levels were reduced (approximately 48% and approximately 15% of control, respectively). Since SAMDC-overexpressing clones exhibited increased clonogenicity in soft agar, our data suggest that spermine may be selectively involved in conferring a more invasive phenotype to breast cancer cells.
These experiments were designed to test the role of the polyamine pathway in breast cancer progression utilizing an experimental system based on the development of ovary-independent rat mammary tumors and their sequential transplantation into syngeneic hosts. Three key enzymes involved in the PA biosynthetic/catabolic pathway (ornithine-decarboxylase (ODC), S-adenosylmethionine decarboxylase (SAMDC), and spermidine/spermine N'-acetyltransferase (SSAT)) were measured in tumors at different stages of progression. The most significant finding was the association between increased ODC activity and the acquisition of a hormone-independent, poorly differentiated phenotype. SSAT levels tended to be higher in hormone-independent tumors and, in this tumor category, they tended to be positively correlated with differentiation. However, significant interaction between hormone dependence and differentiation status on SSAT expression prevented reliable assessment of the possibly complex role of this enzyme in tumor progression. Neither hormone dependence nor differentiation status were correlated with SAMDC levels. We conclude that, among the three enzymes tested, ODC overexpression is the most significant alteration in the PA metabolic pathway associated with breast cancer progression in this experimental system.
To determine the direct influence of the polyamine (PA) pathway on breast cancer phenotype, we employed a transfection approach to induce overexpression of the PA biosynthetic enzyme ornithine decarboxylase (ODC) in the hormone-responsive MCF-7 breast cancer cell line. Using a modified calcium phosphate method and an ODC cDNA coding for a truncated and more stable enzyme, we were able to achieve a moderate to marked degree of ODC overexpression (up to 150-fold) in a transient transfection system. ODC-overexpressing MCF-7 cells exhibited a selective increase in cellular putrescine content, while the levels of spermidine and spermine remained unaffected. Under defined culture conditions, overexpression of ODC resulted in a consistent but modest increase in [3H]thymidine incorporation into DNA which was similar in the presence and absence of 17-beta-estradiol, TGF-alpha, and IGF-I. In the presence of serum, the effect of ODC overexpression on basal [3H]-thymidine incorporation into DNA was inconsistent, possibly as a result of subtle differences in culture conditions. Overall, our results support the hypothesis that activation of the PA biosynthetic pathway may confer a growth advantage to breast cancer cells.
Insulin-like growth factors (IGFs) I and II are potent mitogens for breast cancer cells. Their proliferative activity is likely to be influenced by their binding proteins (IGFBPs), a family of newly identified proteins. We report here on the in vivo hormonal regulation of mRNAs for IGF-II and IGFBPs in the N-nitrosomethylurea-induced rat mammary tumor, a well-established model of hormone-responsive mammary cancer. IGF-II mRNA levels tended to decrease in regressing tumors following ovariectomy, and they markedly increased upon reactivation of tumor growth with hormone repletion. Ovariectomy induced a drastic increase in IG-FBP-6 mRNA which was reversible with hormone repletion. Similar but more modest changes were observed with IGFBP-2 mRNA. In contrast, IGFBP-3 and IGFBP-4 mRNAs tended to decrease with ovariectomy and increase with hormone repletion. These latter effects, however, were modest, variable, and not statistically significant. In situ hybridization analysis revealed that IGF-II, IGFBP-5, and IGFBP-6 mRNAs were localized in the stromal component of the tumor, whereas IGFBP-2 mRNA was expressed by epithelial cells. We conclude that hormonal regulation of IGFBP expression is heterogeneous, thus suggesting divergent biological functions for these peptides. Our data also emphasize the importance of potential stromal-epithelial interactions in the control of breast cancer cell proliferation by IGFs.
Explore the source record for details and available documents.