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Biomedical subjects

R Simon

Publications and source records attributed to R Simon.

At least 271 records · Page 15Linked to original sources
PubMed1991

Heat shock protein hsp72 induction in cortical and striatal astrocytes and neurons following infarction.

Transient global and transient focal ischemia induced the 72 kDa heat shock protein (hsp72) in neurons in cortex, striatum, and other regions known to be injured during transient ischemia. A novel finding was the induction of hsp72 in islands (cylinders in three dimensions) of cells composed of astrocytes around the perimeter and neurons in the interior. Since histology showed pale staining in these regions, it is proposed that these islands represent areas of focal infarction in the distribution of small cortical and lenticulostriate arteries. Although the factors responsible for hsp72 induction during ischemia and infarction are unknown, these results suggest differences in mechanisms of hsp72 induction in astrocytes compared to neurons.

Animals↗
PubMed1991

Selecting combinations of chemotherapeutic drugs to maximize dose intensity.

A mathematical model is described for selecting combinations of chemotherapeutic drugs in order to maximize antitumor dose intensity subject to constraints on toxicity to normal organ systems. Determination of which drugs to combine and in what proportions to combine them offers combinatorially huge numbers of possibilities. The method described here offers one approach to identifying combinations worthy of evaluation in prospective comparative clinical trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Quaternary ammonium compounds as structural probes of single batrachotoxin-activated Na+ channels.

Quaternary ammonium (QA) blockers are well-known structural probes for studying the permeation pathway of voltage-gated K+ channels. In this study we have examined the effects of a series of n-alkyl-trimethylammonium compounds (Cn-QA) on batrachotoxin (BTX)-activated Na+ channels from skeletal muscle incorporated into planar lipid bilayers. We found that these amphipathic QA compounds (Cn-QA where n = 10-18) block single Na+ channels preferentially from the internal side with equilibrium dissociation constants (KD) in the submicromolar to micromolar range. External application of amphipathic QA compounds is far less effective, by a factor of greater than 200. The block can be described by a QA molecule binding to a single site in the Na+ channel permeation pathway. QA binding affinity is dependent on transmembrane voltage with an effective valence (delta) of approximately 0.5. QA dwell times (given as mean closed times, tau c) increase as a function of n-alkyl chain length, ranging from approximately 13 ms for C10-QA to 500 ms for C18-QA at +50 mV. The results imply that there is a large hydrophobic region within the Na+ channel pore which accepts up to 18 methylene groups of the Cn-QA cation. This hydrophobic domain may be of clinical significance since it also interacts with local anesthetics such as cocaine and mepivacaine. Finally, like BTX-activated Na+ channels in bilayers, unmodified Na+ channels in GH3 cells are also susceptible to QA block. Amphipathic QA cations elicit both tonic and use-dependent inhibitions of normal Na+ currents in a manner similar to that of local anesthetic cocaine. We conclude that amphipathic QA compounds are valuable structural probes to study the permeation pathway of both normal and BTX-activated Na+ channels.

Animals↗
PubMed1991

Management of transperitoneal gunshot wounds of the spine.

To evaluate the results of a conservative approach to gunshot wounds of the spine with a transperitoneal trajectory, we analyzed our 4-year experience with 21 patients. The management protocol consisted of standard treatment of the intra-abdominal injuries, vigorous irrigation of the missile track, and a 48-hour course of antibiotic therapy. The lumbar spine was involved in 14 patients (67%) and the thoracic spine was injured in seven (33%). Eleven patients (52%) were paraplegic on admission and ten patients (48%) had a fixed partial neurologic deficit. One patient with an ISS of 75 died intraoperatively from exsanguination (mortality, 5%). Early morbidity correlated with ISS greater than 40 and spinal AIS greater than 3. Late nonneurologic morbidity was independent of ISS and spinal AIS. One patient required reoperation for a retroperitoneal abscess secondary to a leak from a repaired ureter. Another patient had a retroperitoneal collection on a CT scan which resolved spontaneously. There were no spinal or paraspinal infectious complications in the presence (five cases) or absence of a colonic injury. No change in neurologic status was observed in any patient during a mean follow-up period of 3 months. This preliminary experience suggests that a conservative approach consisting of irrigation of the missile track and short-term antibiotic therapy without laminectomy or removal of fragments from the spinal canal yields optimal results without increasing infectious complications of the spine.

Abdominal Injuries↗
PubMed1991

Isolation and characterization of insertion sequence elements from gram-negative bacteria by using new broad-host-range, positive selection vectors.

On the basis of an RSF1010-derived broad-host-range vector, three different systems which enable positive detection and isolation of insertion sequence (IS) elements from gram-negative bacteria were constructed. Vectors pSUP104-pheS, pSUP104-rpsL, and pSUP104-sac were used successfully in a number of Rhizobium strains and in Xanthomonas campestris. More than 20 different IS elements were isolated and characterized. The 16 IS elements from Rhizobium meliloti were further used to characterize various R. meliloti strains by hybridization. The resulting hybridization patterns were different for every strain and gave a clear and definite IS fingerprint of each strain. These IS fingerprints can be used to identify and characterize R. meliloti strains rapidly and unequivocally, as they proved to be relatively stable. Some of the IS elements were found to be identical when the IS fingerprints from a given strain were compared. This method of IS fingerprinting can also establish whether IS elements are the same, related, or different.

Blotting, Southern↗
PubMed1991

When to randomize?

Many clinical trials address the question of the duration of therapy or whether initial therapy can be improved by the addition of a consolidation or maintenance regimen. For such clinical trials, the question of when to perform the randomization is often difficult. Conventional statistical wisdom prescribes that randomization should take place as late as possible before treatment is effected. This is not always possible or desirable, however. In this report, we describe the factors that are influenced by the timing of randomization, quantify how timing affects these factors, and attempt to provide a tool to help investigators and statisticians determine the appropriate time to randomize for individual studies and particular circumstances.

Randomized Controlled Trials as Topic↗
PubMed1991

Bayesian subset analysis.

As a means of assessing the importance of variation in treatment effect among patient subsets, we derived posterior distributions for subset-specific treatment effects. The effects are represented by combinations of terms for treatment and treatment-by-covariate interaction effects in familiar regression models. Exchange-ability among the interactions is a key assumption; thus, the results are of interest primarily in the context of examining a collection of subsets with no definite a priori distinction relative to treatment effect. Exchangeability leads to a shrinking of the posterior distributions of the interaction terms toward the natural origin of 0, offsetting the tendency of the estimated effects to disperse. The method is applied to parameter estimates from a proportional hazards regression analysis of survival data from a clinical trial, invoking the approximate multivariate normal distribution of the estimates. No subjective prior distributions are required. Vague priors are used for all of the regression coefficients except the treatment-by-covariate interactions, which are assumed to follow a normal distribution.

Clinical Trials as Topic↗
PubMed1991

"Directed" emergency room thoracotomy: a prognostic prerequisite for survival.

The results of 163 patients (49 SWs, 85 GSWs, 29 blunt trauma) who had resuscitative thoracotomy in the emergency room (ERT) were reviewed to reassess the indications for the procedure. The Revised Trauma Score (RTS) of the patients ranged from 0 to 3 in 138, 4 to 8 in 21, and greater than 8 in four. No patient with blunt trauma survived. Sixteen patients [12 (24.5%) with stab wounds and 4 (4.7%) with gunshot wounds] were eventually discharged, an overall survival of 9.8%. Eight of the survivors were without vital signs on arrival at the emergency center and one of them had only signs of life at the scene. Survival was best when the site of penetration was thoracic (n = 84) and the ERT was "directed" at potential cardiac injury. Fifty-six of these patients (66.6%) did have cardiac wounds with tamponade and 12 of them survived (21.4%). Two of the remaining 28 patients, both with pulmonary injury, were salvaged. This was significantly (p less than 0.001) higher than in patients with head and neck (n = 4), abdominal (n = 19), or multiple site (n = 40) injury when the ERT was nondirected. Two of the five patients (40%) with extremity vascular injuries survived after ERT was successful in restoring a cardiac rhythm. These data suggest that in patients without vital signs, ERT "directed" at potential cardiac injury based on thoracic penetration is an important prognostic prerequisite for survival. Emergency room thoracotomy is not beneficial in blunt trauma and its role in penetrating abdominal injuries remains unproven.

Adult↗
PubMed1991

[Dose and time dependence of hemodynamic tolerance development during intravenous nitrate therapy in acute myocardial infarct].

Intravenous nitroglycerin therapy during acute myocardial infarction has beneficial effects on infarct size, infarct complications, and mortality. Numerous dosage formulas for the continuous administration of nitrates are currently used, although several studies have demonstrated the rapid development of tolerance during long-term treatment in patients with ischemic heart disease. The dose and dosage of a continuous nitrate application in the clinical setting of acute myocardial infarction has thus yet to be resolved. This study investigated the hemodynamic effects of a 60-h, low- (33 micrograms/min) vs high- (133 micrograms/min) dose intravenous nitroglycerin (NTG) infusion in 16 patients with uncomplicated acute myocardial infarction. In group I (33 micrograms/min NTG; n = 8) the initial nitrate effect on the pulmonary capillary pressure (PCP-control: 14 +/- 1.5; 4 h: 7 +/- 0.9; 60 h: 7 +/- 0.8; mean +/- SEM; all values in mm Hg) and mean pulmonary artery pressure (PAPM-control: 23 +/- 2.3; 4 h: 15 +/- 1.3; 60 h: 14 +/- 1.3) remained unchanged for 60 h. In group II (133 micrograms/min NTG; n = 8) an almost complete loss of the initial effect on PCP (control: 15 +/- 1.6; 4 h: 5 +/- 1.4; 60 h: 12 +/- 1.3) and PAPM (control: 25 +/- 2.0; 4 h: 14 +/- 1.8; 60 h: 20 +/- 1.3) was observed. In contrast to high-dose application the low-dose NTG-infusion induced comparable acute hemodynamic effects that were not attenuated by tolerance development.

Aged↗
PubMed1991

[Flexible aortic valve prostheses: long-term functional results with porcine bioprostheses without mechanical commissure stent and aortic homografts].

The long-term performance of two different types of flexible aortic prostheses was evaluated in 10 patients who received a stentless porcine prosthetic valve (group A) and in 18 patients who underwent aortic valve replacement with an aortic homograft (group B). In group A early postoperative angiography (5-16 days post surgery) revealed a mean gradient across the aortic prosthesis of 8 +/- 6 mmHg. Late postoperative Doppler echocardiography (3.2 +/- 0.9 years post surgery) suggested a mean gradient of 6 +/- 3 mmHg with a Doppler derived valve orifice area of 1.8 +/- 0.6 cm2. Color Doppler visualized mild prosthesis regurgitation in two of the 10 patients and two-dimensional imaging showed no significant leaflet calcification. In group B late postoperative Doppler echography (5.2 +/- 1.6 years post surgery) suggested a mean gradient of 11 +/- 14 mmHg with a mean graft orifice area of 1.8 +/- 0.5 cm2. Color Doppler revealed prosthesis regurgitation in 15 patients (severe 1, moderate 2, mild 12) and two-dimensional imaging visualized significant prosthesis leaflet calcification in two patients. The good hemodynamic function of a stentless porcine bioprosthesis which seems to be preserved for at least several years indicates that the use of the flexible aortic xenograft is worthwhile pursuing. The long-term performance of an aortic homograft is relatively poor and may be due to unsolved problems with regard to sterilizing and storing the valves.

Adult↗
PubMed1991

[Percutaneous, transluminal angioplasty of aortocoronary venous bypass grafts--acute success, angiography and clinical follow-up].

In 41 consecutive patients with 49 stenoses of aorto-coronary venous bypass (ACVB) grafts percutaneous transluminal angioplasty (PTA) was attempted. PTA was successful, i.e., the percent area stenosis was reduced by greater than 20% to less than 70% (quantitative measurement with a precision magnifying lens from two orthogonal angiographic views) in 46 stenoses (94%) of 38 patients (93%). In 35 patients (92%) with 42 stenoses control coronary angiography was performed after a mean interval of 189 +/- 186 days. Recurrence, defined as an increase of percent area stenosis to greater than or equal to 70%, was found in nine stenoses (21%) of nine patients (26%). Recurrence correlated with a stenosis length greater than 10 mm before PTA (5/8 vs 4/32 stenoses: p less than 0.01). In recurrent stenoses, the average diameter of the grafted native coronary artery was significantly smaller than in recurrence-free stenoses (1.92 +/- 0.52 mm vs 2.45 +/- 0.50 mm; p less than 0.01). Clinical data were collected from all 38 patients with successful PTA after an average of 30 +/- 17 months following PTA. In this interval, 11 patients had undergone re-angioplasty and eight patients were re-operated; in addition, there were three cardiac deaths. In the 27 surviving patients without re-operation (71%), angina pectoris had improved from a mean of 3.0 +/- 0.7 before PTA to 1.8 +/- 1.0 (CCS-classification) (p less than 0.001). In 19 of the 27 patients (70%) the exercise stress test was negative, in contrast to only three patients (11%) before PTA. Thus, in the majority of patients PTA of ACVB-graft stenoses improves quality of life.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

[Young patient with left brain infarct and transient right sided hemiparesis in cardiac papillary fibroelastoma].

This is a case report of a 25-year-old female with recurrent episodes of transient cerebral ischemia accompanied by transient hemiparesis. Cardiac ultrasound examination revealed a small left-ventricular tumor located between the chordae tendineae. The echocardiographic finding was subsequently confirmed by surgery. The entire tumor was removed and the mitral valve remained intact. Due to the histological and immunohistochemical findings a papillary fibroelastoma was diagnosed. The early and late postoperative course was without event.

Adult↗
PubMed1990

Selecting drug combinations based on total equivalent dose (dose intensity)

We describe a mathematical model for selecting cytotoxic drugs and dosages for a combination regimen based on the antitumor activities of the drugs given as single agents and their organ-specific maximum tolerated doses. The regimen defined maximizes an approximate measure of antitumor effect subject to constraints on combined toxicity. This approach does not assume that the underlying dose-response curve is steep; nor does it assume that maximally dose-intense regimens are clinically appropriate in all situations. Whether the identified regimen is superior to standard treatments should be determined by prospective, randomized clinical trials. Determining which drugs to combine and in what proportions to combine them offers combinatorially huge numbers of possibilities. The method described here offers one approach to identifying combinations worthy of evaluation in prospective trials.

Altretamine↗
PubMed1990

A new family of RSF1010-derived expression and lac-fusion broad-host-range vectors for gram-negative bacteria.

A series of broad-host-range expression and lac fusion vectors, based on RSF1010 derivatives, was constructed. The expression vectors contain various promoters (pNm, plac, ptac and pS1) for expression of foreign genes. The efficiency of the promoters was determined in Escherichia coli, Rhizobium meliloti, Rhizobium leguminosarum and Pseudomonas putida by beta-galactosidase activity measurements. Of the promoters assayed in E. coli, the most effective is the tac promoter, whereas in soil bacteria the appropriate promoter for overexpression of foreign genes is the NmR promoter. The GmR gene, serving as a selectable marker for the plasmids, was efficiently expressed in R. meliloti as revealed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and thus, pGm was also used to construct an expression vector. The translational fusion vectors allow the identification and characterization of promoter-carrying cloned fragments on the translational level, whereas the transcriptional fusion vectors can be used to identify and to study promoters on cloned fragments. All lac fusion vectors contain the E. coli lacZ gene or the complete lac operon facilitating quantification of expression.

Base Sequence↗