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Biomedical subjects

D H Schmidt

Publications and source records attributed to D H Schmidt.

At least 19 recordsLinked to original sources

Preclinical evaluation of a radiosensitizing effect of gemcitabine in p53 mutant and p53 wild type bladder cancer cells.

OBJECTIVES: Despite clinical use, the radiosensitizing effect of gemcitabine (2'2'-difluorodeoxycytidine) in human transitional cell carcinoma (TCC) has not been shown to date. We investigated gemcitabine as a radiosensitizer for human TCC cells. METHODS: Monolayer cultures of RT112 (G1, p53 wild type), RT4 (G1-G2, p53 wild type), T24 (G3, p53, mutant type), and SUP (G4, p53 mutant type) cells were incubated in medium with gemcitabine. Electron beam radiation was applied alone, simultaneous, or 3, 6, 12, and 24 hours after gemcitabine. Jurkat leukemia cells were used as controls for radiation toxicity. Cell survival was determined 6, 12, 24, 48, and 72 hours after radiation by microculture tetrazolium assay. DNA damage was evaluated by flow cytometric assessment of poly(ADP-ribose) polymerase, and apoptosis was determined by terminal-deoxynucleotidyltransferase-mediated dUTP nick-end labeling and flow cytometric assessment after annexin-V and propidium iodide labeling. RESULTS: In all TCC cell lines, radiation alone caused only little and insignificant growth inhibitory effects at 10 Gy. Gemcitabine alone had a dose-dependent cytotoxic and apoptosis inducing effect on all TCC cell lines independent of p53 status. Assays combining radiation with gemcitabine in different dose and time schedules demonstrated no radiosensitizing effect in TCC cells. CONCLUSIONS: Gemcitabine is effective in TCC cell lines independent of p53 status. A radiosensitizing effect could not be demonstrated. Again, p53 status was not predictive of the radioresponse in the bladder cancer cell lines. Clinical studies with gemcitabine and radiotherapy might nevertheless yield different results but should be performed with utmost caution.

Animals↗

Validation of Doppler FloWire for measurement of coronary flow reserve in humans.

Previous studies have validated the 133Xenon (133Xe) method to assess regional myocardial blood flow and coronary flow reserve (CFR). Doppler FloWire (DFW) has been used recently for measuring CFR to assess the physiological significance of coronary stenosis. Data obtained by DFW has never been correlated to 133Xe. Our study compared data from DFW measurement of CFR to that obtained by 133Xe in 31 consecutive patients with variable coronary stenosis. Regional myocardial blood flow was measured by assessing the rate constants of 133Xe washout using multicrystal gamma camera after injection (20 millicuries) in the right or left coronary artery. CFR was assessed by measuring resting and hyperemic coronary blood flow by 133Xe and DFW using i.v. adenosine (140 mcg/k/min x 3 min). CFR was also measured by DFW giving intracoronary (i.c.) adenosine (12 microg in the right coronary, 18 microg in the left). In both methods--133Xe and DFW--coronary flow reserve was defined as the ratio of maximal hyperemic-to-baseline flow. DFW and 133Xe assessment of CFR correlated highly, whether adenosine was used i.c.(r=0.87; P=0.0001) or i.v.(r=0.78; P=0.0001). CFR obtained by DFW following i.c. and i.v. adenosine correlated well (r=0.79; P=0.0001). i.c. adenosine has fewer side effects. Both DFW and 133Xe are comparable in measuring CFR in humans.

Aged↗

On the possible role of reactive oxygen species in angiogenesis.

Human microvascular endothelial cells grown on a 3-D reconstituted extracellular matrix (Matrigel) spontaneously and rapidly form a capillary network of tubular structures, thus modeling part of the angiogenic cascade. Exposure of the cells at the time of plating onto Matrigel to a brief episode of hypoxia (40-60) min and subsequent reoxygenation, significantly accelerated (up to 3-fold) the rate of tubular morphogenesis, as determined by computer-aided morphometry. This effect was not dependent on activation of PKC or upregulation/release of angiogenic growth factors. Rather, hypoxia/reoxygenation (H/R), but not hypoxia alone, caused the formation of reactive oxygen species (ROS) and the activation of the nuclear transcription factor NF kappa B, both of which were inhibited by ROS-scavengers, such as pyrollidine dithiocarbamate. Tube formation was inhibited, also under normoxic conditions, by diverse ROS antagonists in a dose-dependent fashion. Our results indicate that angiogenesis is accompanied by and/or requires generation of ROS. We hypothesize that in the clinical setting of hypoxia/reoxygenation during ischemic pre-conditioning, enhanced activation of ROS-dependent intracellular signaling may accelerate the rate of neovascularization also in vivo, thus contributing to the alleviation of certain ischemic lesions.

Cell Hypoxia↗

Cardiomyoplasty after implantation of a pacemaker and cardioverter/defibrillator.

Presently, a combination of two surgical methods improves the survival of patients with advanced ventricular dysfunction: implantable cardioverter/defibrillator implantation (which prevents sudden cardiac death) and cardiomyoplasty (which prevents further dilatation of the heart and provides additional cardiac assistance). We report the clinical course of a patient who had cardiomyoplasty after cardioverter/defibrillator implantation and pacemaker insertion. It is a rare case in which three different devices cardioverter/defibrillator, pacemaker, and cardiomyostimulator) are functioning together without crosstalk.

Adult↗

Left ventricular function during exercise testing and training.

Left ventricular function (LVEF) deteriorates during incremental exercise (GXT) in patients with ischemia (+ISCH). Left ventricular (LV) functional response during steady-state exercise, typical of that used in exercise training, are unknown. We compared LVEF in patients with documented coronary heart disease (CHD) who either had (+) or did not have (-) ISCH, and in healthy volunteers (CONTROL) during GXT and steady state. First pass RNA was performed during upright cycle GXT at rest (R), at the ventilatory threshold (VT), and at maximal exercise (Max); and during steady state at the workload associated with VT after 10, 20, and 30 min of exercise. RNA allowed measurement of ejection fraction (EF) and wall motion (WM); ISCH was mild, angina being relieved by momentary reductions in workload during steady state. Although +ISCH demonstrated the expected deterioration in LV function during GXT (decreased EF, abnormal WM)(EF = 58 to 56 to 54%), there was no evidence for progressive deterioration of LV function during steady state despite the presence of mild ISCH (56 to 56 to 54 to 54%). In -ISCH and CONTROL there were normal responses of EF during GXT (43 to 51 to 51% and 59 to 65 to 61%) and steady state (43 to 51 to 53 to 51% and 59 to 65 to 68 to 69%). We conclude that mild ischemia may be tolerated during steady-state exercise at levels consistent with exercise training without progressive deterioration of LV function.

Adult↗

Congenital clavicular pseudoarthrosis associated with vascular thoracic outlet syndrome: case presentation and review of the literature.

Thoracic outlet syndrome (TOS) associated with congenital clavicular pseudoarthrosis is rare in adults and often misdiagnosed. In this case report, we describe an adult female who was found to have thrombosis of the subclavian and axillary arteries with embolization documented by invasive angiography. This unusual vascular manifestation of TOS should remind physicians that anatomic derangements may predispose to upper extremity ischemia.

Adult↗

Coronary air embolism: incidence, severity, and suggested approaches to treatment.

Because no well-controlled study of inadvertent coronary air embolism has been done to truly quantify the incidence of this cardiac catheterization complication, we wanted to determine its incidence and severity in an active teaching medical center and assess approaches to treatment. We retrospectively reviewed 3,715 coronary angiogram and PTCA reports performed over 32 months. Further, we classified severity based on angiographic findings and symptoms as minimal, mild, moderate, and massive. Two independent angiographers reviewed 764 consecutive cines performed in the first 2 months of training of each new fellow and 740 cines performed in the last 2 months of training. We found that during the first 2 months of training the overall incidence for significant intracoronary air embolism was 0.19% (7 documented cases) compared with 0.2% (3 cases) for non-reported, minimal asymptomatic air embolism. The estimated incidence for total air emboli events was 0.27% (10/3,715). We did not find coronary air emboli in the 740 cines performed at the end of fellowship training. Additionally, the incidence of coronary air emboli during PTCA training was much higher compared with coronary angiography training (0.84 vs. 0.24%). Although there is no best technique to restore blood flow after blockage by air emboli, we suggest as options aspirating the air or forcefully injecting saline, with auxiliary supportive measures like 100% oxygen, IABP, CPR, and DC cardioversion.

Aged↗

Transesophageal echocardiographically guided atrial transseptal catheterization in patients with normal-sized atria: incidence of complications.

The incidence of cardiac complications from atrial transseptal catheterization has never been quantified in patients with normal-sized atria. Series defining the complication rate are derived from diseased hearts with structural changes that may alter the complication rate of the procedure. The generation of a standardized incidence of perforation in a population of structurally normal atria has important implications. A total of 46 atrial transseptal catheterizations guided by transesophageal echocardiography (TEE) for radiofrequency ablation of left-sided accessory pathways was performed in 42 patients during a 3-year period (1990-1993). Clinical and echocardiographic data were analyzed, with special attention given to TEE reports pre- and post-transseptal catheterization. Only one complication occurred in the 46 procedures (2.2%): a perforation of the left atrium that led to pericardial effusion and cardiac tamponade. In a small series of patients with normal sized atria, we have demonstrated that TEE-guided transseptal catheterization in a procedure with a low complication rate.

Adult↗

Fee-for-service versus capitation-based reimbursement: how the payment method affects utilization of echocardiographic services by referring physicians.

Historically, health insurance carriers (HIC) have reimbursed physicians on a fee-for-service basis for echocardiographic studies. With the emergence of managed care, the HIC now may have the option of paying on a capitation basis. To determine whether the method of reimbursement had any bearing on the types of patients referred for echocardiographic services, we conducted a two-phase (retrospective) study. In Phase One, we assessed two groups of ambulatory patients with regard to patient characteristics, medical reason for referral, and echocardiographic results. Group A (4,066 patients) had insurance plans that stipulated reimbursement for echocardiographic services as part of capitation for cardiology services. Group B (3,061 patients) had plans that reimbursed for echocardiographic services on a fee-for-service basis. In Phase Two, we assessed a total of 5,947 patients (3,833 from Group A and 2,114 from Group B) over a period of 40 months to determine the frequency of referral for a second echocardiogram within 2 years of a normal one and the repeat normalcy rate. The results showed that the capitation reimbursement group included younger, predominantly female patients who were referred more often for a more benign reason and who more frequently were diagnosed echocardiographically with less severe disease, higher rates of normalcy, and repeat normalcy. These findings suggest that in our geographic area the capitation method of reimbursement permitted more liberal utilization of echocardiographic services. In this era of cost awareness, the study suggests the need for better screening of patients referred for echocardiographic services.

Capitation Fee↗

Percutaneous balloon aortic valvuloplasty in high-risk elderly patients.

From 1987 to mid-1994 we performed 16 percutaneous balloon aortic valvuloplasties. All patients (mean age 80 years; 53% female, 47% male) had significant congestive heart failure from aortic valve stenosis; the majority were categorized as New York Heart Association Class IV (shortness of breath at rest). Twelve patients were not surgical candidates; four patients refused surgery. After valvuloplasty, all patients became asymptomatic (NYHA Class I & II), the average preprocedure valvular gradient of 59 mm Hg decreased to 31 mm Hg, and valve area increased from 0.8 cm2 (0.3 cm2-0.98 cm2) to 1.3 cm2 (0.6 cm2-1.44 cm2). The only complications were two minor groin hematomas (2 patients). Within 6 months, 50% of the patients were symptomatic again; the overall survival rate was 23 months. We conclude that in the proper environment this procedure can be effective and safe--even in high-risk elderly patients. Although symptom improvement is transient, valvuloplasty provides a valuable opportunity to treat intercurrent medical conditions and possibly follow up with surgery.

Age Factors↗

Left ventricular ejection fraction during incremental and steady state exercise.

Despite extensive study of left ventricular (LV) function during incremental exercise (INC), there is little known about LV function during steady state exercise typical of that used during exercise training. In this study we evaluated LV ejection fraction (LVEF) during upright cycle ergometer exercise using first-pass radionuclide angiography (RNA). Healthy volunteers (N = 10) were studied during both INC and steady state. INC studies were performed at rest, at the ventilatory threshold (VT), and at maximal exercise. During steady state studies were performed after 10, 20, and 30 min of exercise at VT. During INC LVEF increased from rest (61% +/- 5%) to exercise at the VT (73% +/- 5%). There was no further change in LVEF at maximal exercise (73% +/- 5%). During steady state, LVEF increased from rest (61% +/- 5%), to exercise at VT (73% +/- 5%), with further increases after 20 (78% +/- 6%) and 30 (79% +/- 3%) min of exercise. The results suggest that LVEF is nearly maximal during submaximal exercise at VT. During steady state LVEF continues to increase with continuation of steady state exercise.

Adult↗

High incidence of renal artery stenosis in patients with coronary artery disease.

The incidence of renal artery stenosis (RAS) in patients with coronary artery disease (CAD) has not been well documented. Over a 9-month period, 196 patients who underwent coronary angiography because of clinically suspected CAD had routine nonselective renal cine or digital subtraction angiography. There were 68 females and 128 males with a mean age of 63 years (range 35-85). Angiographically significant CAD was present in 152 patients (78%). Of the total patient cohort, 29 patients (15%) had mild RAS (< 50%), and 36 patients (18%) had significant RAS (> or = 50%). In patients with normal coronary arteries, only three patients (7%) had RAS. Thirty-three patients (92%) with severe RAS also had CAD. Of these 33 patients, 45% had hypertension, 30% had hyperlipidemia, 24% had diabetes mellitus, 24% had renal insufficiency (creatinine > or = 1.5), and 51% were smokers. In addition, it was noted that 20 of these patients (61%) had two or more of the above-listed clinical parameters. However, univariate analysis using the chi-square test revealed that only CAD (22% P < 0.03) and renal insufficiency (29% P < 0.15) were reliable clinical predictors of RAS. In conclusion, RAS is a frequent finding in patients with CAD, particularly when renal insufficiency is also present.

Adult↗

Utilization of the Wallstent for the treatment of innominate vein obstruction: a case report.

Debilitating obstruction of the large veins may occur from external compression, neointimal proliferation or thrombosis. Appropriate interventions are contingent upon the underlying etiology and the local vascular anatomy. A case of innominate vein obstruction is presented illustrating the available intravascular therapeutic options, with special emphasis placed on intravenous stenting.

Aged↗

Evaluating the flow characteristics of artificial pumping devices using nuclear scintigraphy.

The design and development of artificial blood pumps require qualitative and quantitative data relative to pump filling, ejection, and wall motion in order to optimize the design and maximize the pattern of blood flow through the pump. To assist in the development of an artificial heart, we utilized radionuclide scintigraphy and a high-resolution gamma camera to evaluate the flow patterns through the pump. We performed a comparative analysis of the flow patterns in a pneumatically driven ventricular assist device (Sarns/3M VAD) and the electrically driven Milwaukee Heart. These analyses disclose some significant differences between the two devices with regard to the blood sac compression patterns and ejection as well as valvular regurgitation. On the basis of these findings, nuclear scintigraphy for analyzing fluid shear stress and flow dynamics seems a useful technique for evaluating blood flow through artificial blood pumps. Because the procedure does not require a translucent casing or direct contact with the device being studied, it would be especially useful in evaluating artificial blood pumps implanted in patients with heart failure.

Coronary Circulation↗

Transesophageal echocardiography with a single-plane probe. Long-axis views of the heart from the apical (transgastric) approach.

The literature suggests that during transesophageal echocardiography (TEE), a short-axis view can be obtained in the gastric position using a single-plane probe. Recently, we have found that a long-axis apical display of the heart can be achieved by placing the tip of the probe in the fundus of the stomach. In a 3-month period, we attempted to obtain this view in 54 consecutive patients. Twelve of the patients had TEE done under general anesthesia, while the other 42 patients had the procedure performed under sedation with midazolam at hospital bedside or as an outpatient. The long-axis transgastric view was obtained in 51 of the 54 patients (94%). The image quality was graded subjectively as good in 39 (72%) and fair in the other 12 patients (22%). This view helped to establish the diagnosis in eight patients (15%) and to increase the level of confidence about the accuracy of the diagnosis in 23 (43%) other patients. Four patients' findings are described. We conclude that the new long-axis transgastric view is easy to obtain, does not add much time to the usual TEE study, does not add to the low complication rate of TEE, and may help to interrogate the distal structures of the heart.

Adolescent↗

Left ventricular volume calculation using a count-based ratio method applied to first-pass radionuclide angiography.

Most count-based radionuclide methods for calculating left ventricular volume rely on measurement of radioactivity in a peripheral blood sample and a measurement of ventricle to collimator distance. We have developed a method which requires neither a blood sample nor a distance measurement and which is applicable to first-pass radionuclide angiography. The parameters used to calculate volume are the area of pixel, the total counts in the left ventricle and the maximum pixel count. The equation was used to calculate the volumes in 50 patients who had both resting first-pass radionuclide angiography (25 patients with a single crystal and 25 patients with a multicrystal camera) and contrast ventriculography on the same day. Correlation coefficients for end-diastolic and end-systolic volumes showed r ranging 0.93-0.98 and standard error of estimate ranging 23-35 ml for end-diastolic volume (14%-17% of mean end-diastolic volume) and 16-23 ml for end-systolic volume (18%-21% of mean end-systolic volume). Image processing software for extracting the needed values is generally available on most commercial nuclear medicine imaging systems and the additional time for the calculations is short. Although the theory is based on multiple assumptions, the volume calculation appears to be reasonably accurate and clinically applicable.

Adult↗