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Biomedical subjects

R Simon

Publications and source records attributed to R Simon.

At least 235 records · Page 13Linked to original sources
PubMed1993

[Right ventricular involvement in infero-posterior myocardial infarct: clinical significance of ECG diagnosis].

Right ventricular infarction accompanies acute inferoposterior myocardial infarction in 25 to 53% of cases, the frequency depending on the diagnostic method used. Involvement of the right ventricle can be reliably diagnosed in the right precordial leads of the ECG. Sensitivity and specificity are above 90% and the positive predictive value is over 80%. To assess the clinical value of this extended ECG diagnosis, we retrospectively studied 144 patients with acute inferoposterior myocardial infarction. Right precordial ECG leads V2R to V6R were registered routinely in all of these patients immediately after their admission to the hospital. We found characteristic ECG changes of right ventricular infarction in 31 (22%) of these 144 patients: ST elevation of > or = 0.5 mm in the right precordial leads, especially in lead V4R. In this group of patients the following hemodynamic parameters were registered in a significantly higher percentage: biventricular heart failure (29% vs 4%, p < 0.001), isolated right ventricular failure (23% vs 0%, p < 0.002), arterial blood pressure < 90 mm Hg (48% vs 23%, p < 0.001), cardiogenic shock (13% vs 4%, p < 0.05). Furthermore, the following arrhythmias were found significantly more frequently: sinus bradycardia (42% vs 24%, p < 0.05), AV block II type Mobitz 2 and AV block III (22% vs 5%, p < 0.005). Because of hemodynamic disturbances we had to substitute volume more often (39% vs 1%) or employ catecholamines more frequently (39% vs 6%, p < 0.01). Following high degree AV block we inserted a temporary pacemaker in a higher percentage (13% vs 5%) without reaching statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Children and cancer. A perspective from the Cancer Therapy Evaluation Program, National Cancer Institute.

The Cancer Therapy Evaluation Program, National Cancer Institute (CTEP, NCI) strongly supports the role of controlled clinical trials in improving the care of children with cancer, and particularly the central role that the pediatric Cooperative Groups play in this process. Trends that threaten the ability to perform these trials include the increasingly limited financial resources available for clinical investigations and the sentiment within some circles that controlled clinical trials may be inappropriate for ethical reasons. The inherent risks of accepting a new therapy without rigorous comparison to existing therapy strongly support the need for randomized trials with adequate accrual to answer important therapeutic questions in a timely and reliable fashion. Retrospective analysis of multiple clinical trials is one method for identifying compelling hypotheses to be tested prospectively. Using this method, we have demonstrated the association between doxorubicin dose intensity and positive response and outcome for patients with Ewing sarcoma and osteosarcoma, thereby providing direction for the selection of important therapeutic questions to be addressed in future clinical trials for these malignancies.

Antineoplastic Agents↗
PubMed1993

Ischemia-induced regional wall motion abnormality is improved after coronary angioplasty: demonstration by dobutamine stress echocardiography.

OBJECTIVES: The purpose of this study was to examine whether dobutamine stress echocardiography can detect reversal of ischemia-induced left ventricular regional wall motion abnormality immediately after percutaneous transluminal coronary angioplasty. BACKGROUND: Although angioplasty is routinely performed as a means of coronary revascularization, at present there is a question whether this results in an immediate improvement in ischemia-induced left ventricular regional function. METHODS: Thirty-five patients underwent dobutamine stress echocardiography 24 h before and 24 to 48 h after angiographically successful coronary angioplasty. Only patients with normal wall motion at rest were included. Dobutamine infusion was begun at 5 micrograms/kg per min and increased at 5-min intervals (10, 20, 30, 40 micrograms/kg per min). Echocardiographic images were stored into cine loops and analyzed off line with simultaneous comparison of images acquired at baseline, 5 micrograms/kg per min, peak infusion and recovery. Echocardiographic images were interpreted independently, without knowledge of other data, by two experienced cardiologists using the 16-myocardial segment model. RESULTS: Before angioplasty, dobutamine stress echocardiography induced wall motion abnormalities in 31 patients (88%). Wall motion score at peak dobutamine infusion improved in 28 (90%) of the 31 patients after angioplasty. Wall motion score at peak dobutamine infusion for the group improved from 20 +/- 3 before angioplasty to 17 +/- 2 after angioplasty (p < 0.001). There was no change in the rate-pressure product achieved for the group before and after angioplasty (20,038 +/- 6,415 beats/min x mm Hg before versus 20,775 +/- 5,435 after angioplasty, p = NS). Before angioplasty, dobutamine stress echocardiography induced angina in 13 patients (37%), whereas angina occurred only once after angioplasty. Electrocardiographic changes diagnostic of ischemia occurred seven times, all before angioplasty. CONCLUSIONS: We conclude that dobutamine stress echocardiography is an excellent method to demonstrate an immediate improvement in stress-induced regional left ventricular dysfunction in the distribution of the vessel undergoing successful angioplasty.

Angioplasty, Balloon, Coronary↗
PubMed1993

Use of biodegradable (PGA) fabric for repair of solid organ injury: a combined institution experience.

A fabric constructed of biodegradable mesh was used in the operative repair of injured intra-abdominal organs in 60 patients at two Level I Trauma Centres. Splenorrhaphy was performed in 44 patients, hepatorrhaphy in eight, renorrhaphy in five and one combined repair of spleen and liver and one kidney and liver. The age range for the patients was 5 to 61 years. Multiple-organ injury occurred in 21 patients. Mean emergency room systolic BP for the patient series was 120 +/- 24 mmHg (SD), Glasgow Coma Scale 14.3 +/- 1.9, haematocrit 37.2 +/- 6.4 per cent, Injury Severity Score (ISS) 28.1 +/- 16.3, Abdominal Trauma Index (ATI) 15.5 +/- 7.5. Postoperative complications occurred in 36.7 per cent of patients. Time for the operation averaged 165.1 + 72.1 min and preoperative and operative transfusion volume averaged 2248 ml. There were three deaths (5.4 per cent). The mesh organ repair technique is an alternative to conventional surgical procedures used to control bleeding from injured organ surfaces and to close organ parenchymal defects.

Abdominal Injuries↗
PubMed1993

Dose intensity analysis in advanced ovarian cancer patients.

To determine if chemotherapy dose intensity influences treatment outcome in advanced ovarian cancer, all randomised studies of first line chemotherapy, published between 1975 and 1989, were analysed for relationships between planned dose intensity and (a) objective response and (b) median survival. Total dose intensity of each study regimen was calculated and a weighted regression model providing for systemic differences in response or survival among studies was utilised. Hence, treatment arms of different studies were never directly compared. In addition, relative dose intensities of individual drugs within combinations was similarly evaluated. The improvement in objective response rate when adding one unit of total dose intensity ranged between 12% and 16% depending on baseline response rate. The improvement in median survival when adding one unit of total dose intensity ranged between 2 and 4 months. One unit of total dose intensity corresponds to, for example, 20 mg m2 week of cisplatin, or 25 mg m2 week of doxorubicin, or 350 mg m2 week of cyclophosphamide. The analysis of individual drugs suggested that doxorubicin and the platinum compounds were about equally effective, with cyclophosphamide being less effective. The methodological benefits and limitations of the approach used and the implication of the results are discussed.

Antineoplastic Agents↗
PubMed1993

Using the tolerable-dose diagram in the design of phase I combination chemotherapy trials.

PURPOSE: Choosing maximum-tolerated doses (MTDs) of agents to be administered in combination is more complicated than choosing the MTD for a single agent. This is because there are many combinations of doses that will be tolerated. We offer guidance in targeting specific MTD combinations, and suggest trial designs to achieve these targets. METHODS: A graphical method based on a simple, previously described mathematical model is used to guide the phase I trial design. The method involves constructing a tolerable-dose diagram, which displays the toxicities that are expected to occur at various dose combinations. The data required for the method are the single-agent toxicity profiles of the agents. Designs for combinations of taxol with fluorouracil, carboplatin, doxorubicin, cyclophosphamide, and cisplatin are used to demonstrate the methods. RESULTS: For all of the drugs considered here, leukopenia is dose-limiting or nearly dose-limiting. Consequently, no major improvement in total dose-intensity is achievable by combining these drugs. If leukopenia can be eliminated or substantially reduced by use of chemoprotective agents, then a cyclophosphamide/taxol combination appears promising from a dose-intensity point of view. For other combinations, the doses must be reduced from single-agent MTD levels. In the absence of biologic information such as concentrations needed for optimal modulation, it is suggested that single-agent MTDs be reduced approximately proportionately for each drug in the combination. CONCLUSION: Tolerable-dose diagrams are useful for planning phase I trials of combinations of agents. They can suggest which combinations are promising from a dose-intensity perspective, as well as dose-escalation schemes for combinations to be pursued for dose-intensity or other considerations.

Antineoplastic Agents↗
PubMed1993

A multiple-step selection procedure with sequential protection of preferred treatments.

Dunnett (1955, Journal of the American Statistical Association 50, 1096-1121) proposed a one-step many-one test to compare several experimental treatment means with a control. However, after the control treatment is rejected, one would want to make comparisons among the experimental treatments. We assume that there is an order of decreasing preference among the experimental treatments based on other considerations. We propose in this paper a multiple-step selection procedure, an extension of Dunnett's one-step many-one test that will give protection to the preferred treatments and guarantee a high selection probability of the correct treatment when that selection is appropriate. We also provide methods to calculate the sample size required to carry out this test for normal, binomial, and exponential data with random censoring.

Biometry↗
PubMed1993

A study of the dose dependency of a glycine receptor antagonist in focal ischemia.

N-methyl-D-aspartate receptor antagonists are potent neuroprotectants in experimental focal cerebral ischemia, but behavioral and neuropathologic changes seen with these drugs in rodent models may limit the clinical utility of these compounds. Glycine's modulation of N-methyl-D-aspartate channel function offers another pharmacologic approach to excitotoxicity in ischemia. The potent glycine antagonist 7 Chlorothiokynurenic acid (7-Cl-Thio-Kyna) was studied in a permanent middle cerebral artery occlusion stroke model in the rat. The compound was effective, in a dose-dependent manner, in attenuating infarct size when administered before or after permanent middle cerebral artery occlusion. Its activity was mainly due to glycine antagonism inasmuch as 5 Chlorothiokynurenic acid, a compound having other pharmacological activities in common with 7-CI-Thio-Kyna (for instance the radical scavenger action), was inactive in this model. 7-Cl-Thio-Kyna did not produce cytological changes similar to MK 801.

Animals↗
PubMed1993

Structural determinants of quaternary ammonium blockers for batrachotoxin-modified Na+ channels.

Amphipathic quaternary ammonium (QA) compounds are potent blockers of batrachotoxin (BTX)-modified Na+ channels incorporated into planar lipid bilayers. To examine the topology of the QA binding site, we selected two series of QA compounds as structural probes. One series contains two separate hydrophobic moieties but with a common hydrophilic dimethyl QA ion. Most of the QAs within this group bind to BTX-modified Na+ channels with relatively high affinities. For example, benzyldimethyldodecyl ammonium ions, when applied internally, block single, muscle, BTX-modified Na+ channels in bilayers with a one-to-one relationship and display an equilibrium dissociation constant (Kd) of 0.2 microM at +50 mV. Furthermore, the QA dwell times appear to correlate with QA hydrophobic interactions with the channel. These results indicate that there are two large hydrophobic binding domains within the QA binding site. The QAs in the second series contain a hydrophilic head group (trialkylammonium) of variable size but with a common dodecyl hydrophobic tail. Tripropyldodecyl QAs block BTX-modified Na+ channels more effectively (Kd = 0.4 microM at +50 mV) than do trimethyl- and triethyldodecyl QAs, suggesting that the internal Na+ permeation pathway is at least 9 A wide. However, tributyl- and tripentyldodecyl QAs show much lower affinities for BTX-modified Na+ channels at comparable concentrations. These drugs are cut off from binding, probably as a result of the size of their hydrophilic heads (> 10 A), which may be too large to fit in the QA binding site and too bulky to travel freely within the internal permeation pathway. Under whole-cell voltage-clamp conditions, we have further found that BTX-modified Na+ currents in clonal GH3 cells can be blocked by these two series of QA ions, albeit only when the activation gate is open. Closed channels at rest do not bind appreciably with these QA ions. Binding of QA ions is reduced by external Na+ ions in GH3 cells in a manner indicating that external Na+ ions can clear the bound QA ions from the Na+ pore. These results from GH3 cells mirror those obtained with QA blockers in K+ channels of squid axons and suggest that the QA binding domains in BTX-modified Na+ channels and K+ channels may be structurally conserved.

Animals↗
PubMed1993

[Correlation between Doppler echocardiography and invasive determination of left ventricular hemodynamic valve parameters. A comparative study under routine conditions in a cardiology center].

UNLABELLED: Simultaneously performed combined Doppler/catheter studies have shown excellent correlations regarding the comparison of invasively and non-invasively obtained valve gradients. To reflect daily clinical life the current study compared the valve parameters obtained by Doppler echocardiography to those obtained later by catheterization in all consecutive patients who underwent invasive procedure between October 1988 and December 1990. A total of 113 patients was included in the study, 76 with aortic and 37 with mitral stenosis. Regarding the mean aortic valve gradient the following correlations were obtained: all patients: r = .79, patients with an ejection fraction > 50% (n = 59): r = .81, patients with an ejection fraction < 50% (n = 17): r = .67, patients with additional aortic insufficiency (n = 21): r = .77. When the mean mitral valve gradient was compared the correlation was r = .71 for all patients and r = .44 when additional mitral regurgitation was present (n = 10). The comparison of the mitral valve orifice area (n = 30) showed a correlation of r = .58. CONCLUSION: Non-simultaneously performed combined Doppler/catheter studies in unselected patients do reflect daily clinical life, however, correlations are not as good as in corresponding simultaneously performed investigations, thus emphasizing the impact of the study conditions on the final results.

Adult↗
PubMed1992

[An aortopulmonary shunt after a knife wound].

An extensive hemopneumothorax developed in a 23-year-old man after having been knifed in the region of the left nipple. After general surgical care a Bülau suction drain was inserted. Cardiological examination became necessary a week later when a chest X-ray film demonstrated an enlarged cardiac silhouette. Echocardiography revealed pericardial effusion (about 600 ml) which was removed by pericardial aspiration. Cross-sectional and colour Doppler echocardiography showed a shunt between the aorta and right ventricular outflow tract at the origin of the pulmonary artery. At surgery a fistula between the root of the aorta and the pulmonary artery was identified (the posterior sinus near the anulus was nearly completely detached). The fistula was closed and the pulmonary valve reconstructed. The early and late postoperative course was unremarkable.

Adult↗
PubMed1992

[Colonic complications of acute necrotizing pancreatitis].

Among 126 patients operated upon for acute necrotizing pancreatitis in our department over a 10-year period starting in November 1979, 17 had a colonic resection. Colectomy was made mandatory by a necrotic or ischaemic appearance (12 cases, including 3 bowel perforations), an isolated perforation (2 cases) or extensive fat necrosis of the pericolonic atmosphere (3 cases). The hospital mortality was 5 out of the 17 cases. In 6 patients, the pathological results suggested that colonic resection was unnecessary. Since May 1988, a diverting loop ileostomy has been performed whenever colonic viability was found to be dubious at laparotomy. After this policy was introduced no case of secondary colonic complication was encountered. Nevertheless, there still are "abusive" colectomies unjustified by the pathology. Their number should be reduced by a more cautious indication of colonic resection in acute necrotizing pancreatitis.

Acute Disease↗
PubMed1992

Statistical model to determine the relationship of response and survival in patients with advanced ovarian cancer treated with chemotherapy.

BACKGROUND: A statistically appropriate analysis of the association between survival and response measures in patients with ovarian cancer could help to define the role of response rate in planning, monitoring, and interpreting the results of clinical trials. PURPOSE: This study was designed to investigate the relationship between antitumor response determined by clinical or pathological means and survival in patients with advanced ovarian cancer with no previous treatment. We focused on avoiding the limitations of the usual approach of comparing durations of survival for patients responding to therapy with those for nonresponders. METHODS: A new meta-analytic statistical model we developed was used to analyze data from 26 randomized clinical trials published between 1975 and 1989. Our model incorporates intra-study and inter-study sources of variability in the estimates of response and survival. The study also addresses the methodological problems of evaluating response as a surrogate end point and the relevance of this association to clinical decision making and the design of clinical trials. RESULTS: For 13 studies in which response was pathologically assessed, an improvement in surgically documented complete response rate was associated with an increase in median survival. A similar but apparently smaller effect was found for the association between objective clinical response and median survival in the 25 studies reporting these data. CONCLUSIONS: These results suggest that therapeutic measures must produce large improvements in clinical response rates to achieve meaningful effects on median survival. Improvement in surgically documented complete response rate appears to be more strongly associated with increased median survival and, hence, might be used for interim monitoring in clinical trials, but the role of second-look procedures in clinical management is controversial.

Antineoplastic Combined Chemotherapy Protocols↗