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Biomedical subjects

D Marx

Publications and source records attributed to D Marx.

At least 55 records · Page 3Linked to original sources
PubMed1996

Effects of AWD 23-111, a new antiarrhythmic substance, on cardiac conduction and refractoriness.

In isolated spontaneously beating guinea pig hearts, the effects of AWD 23-111 (N-(dicyclohexylcarbamoylmethyl)-N-(3-diethylamino-propyl)-4-nit robenzamid -hydrochloride), a new synthetic class III antiarrhythmic agent with sodium antagonistic properties, were investigated on cardiac electrophysiological parameters, that is, conduction and refractoriness. Concentration-dependent prolongation of the atrioventricular, intraventricular, and His bundle conduction times and of sinus node cycle length were present. At 0.3 microM the repolarization period was prolonged significantly. No reverse use-dependent effect on the repolarization period was observed. During rapid pacing (pacing cycle length = 120 ms for the ventricle and 180 ms for the atrium) the rate-dependent intraventricular (QRS) or atrioventricular conduction time (AVCT) prolongation follows an exponential function of the beat number and is characterized by a drug-specific time constant. The time constant for the intraventricular conduction time prolongation in the presence of 0.1 microM AWD 23-111 was very long at 150 +/- 29 beats (mean +/- SEM; n = 6), indicating a slow binding kinetic to the sodium channel. At 0.1 microM AWD 23-111, a significant increase in the ventricular effective refractory period was reached when the interstimulus interval (S1-S1) was 120 ms and the number of conditioning stimuli (S1) was higher than the time constant. The time constant for the rate-dependent AVCT prolongation in the presence of 0.3 microM AWD 23-111 was 34 +/- 6 beats (n = 6). The effective refractory period of the atrioventricular conduction significantly increased with the number of conditioning stimuli (S1), until the number was comparable with the time constant. In conclusion, AWD 23-111 exerts a wide variety of actions on the cardiac conduction system. Its combined effects on the potassium and sodium channels seem to be responsible for the marked rate-dependent effect on ventricular refractoriness and for the lack of a reverse use-dependency on JT prolongation.

Animals↗
PubMed1996

Preliminary report of data collection in hospital quality assurance programs--a project of the Association of Hospitals of the Czech Republic.

OBJECTIVES: This was the first attempt of the association representing all acute care hospitals in the Czech Republic to collect mutual data which might be used for quality assurance (QA) purposes and which might lead to the development of national standards of care which could be used for hospital accreditation. Data collected included information which was available universally and which could be measured; in addition, information was intended to be similar in each hospital. In most cases, the data collection systems were based on financial information and data had to be identified which might be used for QA purposes, rather than being able to design a system specific for QA purposes. DESIGN: Since the hospital payment system was established in 1992, hospitals have had to develop data collection systems to measure clinical activity; this current study was based on this data collection, adapted to QA purposes. SETTING: The Executive Committee of the Hospital Association agreed to a pilot study of hospitals in 1993; data were collected from approximately 40 hospitals, beginning in 1994. STUDY PARTICIPANTS: Hospitals were chosen based on their ability to collect data and participate in the program, and it was determined that there should be variability in the hospitals, in size, location and activities, but that the data collected should be generic. INTERVENTIONS: Raw data included 33 different items, most of which were irrelevant to QA. Using a computer program, various combinations of data were reviewed and evaluated to ascertain the most appropriate for QA purposes. MAIN OUTCOME MEASURES: Data were chosen for study which included (a) data from the largest departments in the individual hospitals; (b) length of stay for patients hospitalized in these departments; (c) number of occupied beds/physician in the department and (d) mortality/1000 admissions to the department. RESULTS: The combination of (1) a long length of stay; (2) a high occupied bed/doctor ratio; and (3) a high mortality rate/1000 admissions might be indicators of poor quality. Additional factors to consider include: the type of department-emergency, cancer, geriatric, etc.; the nature of the medical activity-acute, referral, primary care, etc.; whether or not "social" beds are included and, generally, comparability among departments. However, as a pilot study, certain indicators can be determined which then can be used for future study to determine quality of care. The ability to cooperate and collect seemingly comparable data indicates reason for optimism in the future; more detailed and accurate studies can be carried out which will enable assessment of the quality of care given in comparable situations in hospitals throughout the Czech Republic.

Accreditation↗
PubMed1996

Expression of Bax in relation to Bcl-2 and other predictive parameters in breast cancer.

BACKGROUND: It has been suggested that modification of the physiological susceptibility to induction of programmed cell death in transformed cells contributes to the pathogenesis of cancer. One of the major regulators of cell death is the bcl-2 family. In breast cancer, altered expression of Bcl-2 has been described. Distribution of its counterpart Bax and the differential expression pattern have still to be evaluated. PATIENTS AND METHODS: Bax expression was investigated by immunohistochemistry in 122 primary breast cancers. Results were correlated with expression of Bcl-2 and other variables of predictive value. RESULTS: There was a positive association between Bax expression and histological grading, (over)expression of c-erbB-1 and -2 and proliferative activity. The correlation was most significant in cases where no concomitant Bcl-2 expression could be detected. In the same subgroup an inverse correlation with positivity for estrogen (and progesterone) receptors was observed. The presence of Bax was not significantly associated with either tumor type and size, nodal status or expression of c-erbB-3. CONCLUSION: Expression of Bax was coupled with negative histopathological features, especially when expression of Bcl-2 was downregulated concomitantly. It may appear that alterations of the differential Bax/Bcl-2 expression pattern take part in deregulation of proliferation and loss of differentiation, thus playing an important role in malignant progression.

Breast Neoplasms↗
PubMed1996

Rate-dependent effects of detajmium and propafenone on ventricular conduction and refractoriness in isolated guinea pig hearts.

Detajmium (4--3'-diethylamino-2'-hydroxypropyl--ajmalin) is an Na(+)-channel-blocking drug with an extremely long recovery from use-dependent sodium channel block. The aim of the present study was to investigate the rate-dependent effects of detajmium on the intraventricular conduction of isolated, spontaneously beating, guinea pig hearts in comparison with the effects of propafenone. Detajmium (0.3 microM) and propafenone (0.3 microM) caused comparable prolongations of the intraventricular conduction time during sinus rhythm. The time to steady state of the rate-dependent QRS prolongation during rapid ventricular pacing follows an exponential function of the beat number after an abrupt change of frequency and is characterized by a drug-specific time constant. This time constant was significantly longer for detajmium (tau = 265 +/- 165 beats; mean +/- SEM; n = 6) than for propafenone (tau = 31 +/- 4 beats; n = 11; p < 0.01). In the presence of propafenone, QRS duration peaked initially before decreasing to a steady state. Detajmium, in contrast, progressively broadened the QRS complex. Both substances caused the greatest increase in the ventricular effective refractory period (V-ERP) when the number of conditioning stimuli (interstimulus interval, 120 ms) was in the range of the time constant. However, when the number of conditioning stimuli was further increased, the V-ERP for propafenone diminished progressively. In conclusion, propafenone displayed, in comparison with detajmium, only a transient rate-dependent effect on intraventricular conduction and V-ERP.

Ajmaline↗
PubMed1996

Temporal changes in function and regional glucose uptake within stunned porcine myocardium.

UNLABELLED: This study compared the effects of porcine myocardial stunning on the uptake of [18F]-fluorodeoxyglucose (FDG) at 24 hr and 7 days after reperfusion. Prior studies in animals subjected to severe myocardial ischemia have shown a sustained increase in FDG uptake relative to perfusion (FDG/MBF). The time course of recovery of FDG/MBF relative to function poststunning, however, has not been well characterized. METHODS: Stunning was induced in eight swine by partially occluding the LAD artery for 20 min. At 1 and 7 days postreperfusion, function was assessed by two-dimensional echocardiography and PET studies were obtained with FDG and either 15O-water or 13N-ammonia. Blood flow by microspheres was determined at baseline, during ischemia and after stunning. Myocardial uptake of FDG relative to blood flow on matching images (FDG/MBF) was calculated for all ROIs and expressed as a ratio of LAD to non-LAD areas. RESULTS: After stunning, left ventricular ejection fraction (LVEF) increased from 42% +/- 10% on Day 1 to 52% +/- 6% on Day 7 (p < 0.05). At Day 1, myocardial blood flow was 0.60 +/- 0.10 ml/min/g in LAD and 0.67 +/- 0.16 in non-LAD regions and neither differed at Day 7. The magnitude of FDG/MBF in the LAD region when normalized to the non-LAD region was 1.29 +/- 0.16 on Day 1 and 1.09 +/- 0.08 on Day 7 (p < 0.05) and was inversely proportional to global measures of LVEF (r2 = 0.61; p < 0.005). CONCLUSION: The severity of postischemic LV dysfunction at 1 and 7 days after stunning correlates with the degree of enhanced regional glucose uptake as estimated by PET. Both normalize within 7 days, suggesting that metabolic and functional abnormalities within completely reperfused myocardium recover in parallel.

Animals↗
PubMed1995

The significance of aggression and impulsivity for self-mutilative behavior.

Self-mutilative behavior (SMB) is presented as a specific form of inwardly directed aggressiveness which is thought to be associated with problems of impulse control. Conceptual problems concerning impulsivity and impulsive aggression are discussed. Among different forms of dyscontrolled behavior, SMB is of special heuristic interest because of distinction can be made between patients committing impulsive and those committing premeditated self-harming actions. Psychometric and biological measures of impulsivity and aggressiveness were assessed in self-mutilators in comparison to depressives and normal probands. Self-mutilators were differentiated into two subgroups, those with an impulsive (ISMB) and those with a premeditated (PSMB) form of SMB, and depressives were also differentiated into two subgroups, those with a history of suicide attempts and those without. Only patients with ISMB (and depressives with a history of suicide attempts) showed an enduring tendency towards dyscontrolled patterns of behavior and cognition; therefore, SMB cannot be generally regarded as an indicator of high impulsivity or an impulse control disorder. Measures of impulsivity and aggressiveness did not behave analogically to each other and aggressive or autoaggressive modes of behavior should not be generally used as an index of impulsivity. A reduction of serotonergic activity, proved by a blunted prolactin response to D-fenfluramine, was found in all patient-groups in comparison to normal probands. Prolactin response after D-fenfluramine challenge turned out to be most blunted among self-mutilators with ISMB and among depressives with a history of suicide attempts.

Adult↗
PubMed1995

Bcl-2 protein expression in breast cancer in relation to established prognostic factors and other clinicopathological variables.

BACKGROUND: Bel-2 inhibits most kinds of programmed cell death and provides a selective survival advantage to various cell types. Bcl-2 is physiologically expressed in ductal epithelia of the normal breast. The biological significance of Bcl-2 (over)expression for the development and progression of breast cancer has still to be evaluated. PATIENTS AND METHODS: A series of 133 primary breast cancers was investigated for expression of the Bcl-2 protein by immunohistochemistry of paraffin-embedded tissue sections. Results were correlated with other variables of established or presumed predictive value. RESULTS: A significant positive correlation was observed between Bcl-2 expression and positivity for estrogen and progesterone receptors (p < 0.001). High proliferative activity as assessed by Ki-67 staining correlated inversely with Bcl-2 expression (p < 0.001). Bcl-2 immunostaining was not related to positivity for c-erbB-1. It was negatively associated with overexpression of c-erbB-2 (p = 0.04), whereas a strong positive correlation was found with expression of c-erbB-3 (p = 0.01). There was a significant inverse correlation between histological grading and immunoreactivity for Bcl-2 (p < 0.001). N0 tumors tended to be Bcl-2 positive, but differences were not statistically significant. CONCLUSION: Bcl-2 was detected predominantly in differentiated tumors. Expression was associated with other favorable histopathological features and predictors of positive clinical outcome. Loss of Bcl-2 expression seems to be linked to loss of hormonal regulatability, increased dedifferentiation and deregulated proliferation.

Breast Neoplasms↗
PubMed1995

EGF-R and overexpression of the oncogene c-erbB-2 in ovarian cancer: immunohistochemical findings and prognostic value.

PURPOSE: The purpose of this study was to investigate the prognostic value of EGF-R (c-erbB-1) compared to the overexpression of the c-erbB-2 oncogene product p185 in ovarian cancer. PATIENTS AND METHODS: The study was conducted on 266 previously untreated ovarian cancer patients with FIGO stage I-IV disease. EGF-R and c-erbB-2 oncogene product p185 have been evaluated using immunohistochemistry. Survival times were analyzed according to the method described by Kaplan and Meier. For the simultaneous evaluation of the prognostic relevance of the analyzed factors, a Cox proportional hazards regression was performed. RESULTS: EGF-R was detected in 13%, and c-erbB-2 oncogene product p185 in 18% of primary tumors. EGF-R showed no significant impact on the survival time, whereas c-erbB-2 oncogene product p185 positive patients had a significantly worse prognosis compared to p185 negative cases (p = 0.002). In the multivariate analysis, c-erbB-2 oncogene product p185, like tumor stage, histological grade and age, was found to be a significant prognostic factor. CONCLUSION: These data confirm the prognostic importance of the c-erbB-2; oncogene product p185 in ovarian cancer at the time of primary surgery, while EGF-R does not seem to have prognostic relevance.

ErbB Receptors↗
PubMed1995

Federal antitrust merger enforcement standards: a good fit for the hospital industry?

We examine the implications of the 1992 Horizontal Merger Guidelines for the hospital industry and subsequent policy statements that were developed for health care providers. Application of antitrust policy to hospitals has raised several concerns, mainly because many communities have few hospitals and economic forces in the industry are accelerating interest in intramarket mergers and provider network development. We address several issues, including the standing of hospitals relative to the market concentration thresholds of the merger guidelines, market concentration compared among challenged and unchallenged mergers of the 1980s, findings of previous research about the relationship between market concentration and competition in hospital markets, and differences in characteristics other than market concentration that are relevant to the merger guidelines among challenged and unchallenged mergers. We found that (1) the specific standards articulated in the merger guidelines do not provide good predictability of when a hospital merger challenge would occur, and (2) comparisons of challenged and unchallenged mergers in similarly structured markets suggest that enforcement actions may deviate in practice from the enforcement principles of the merger guidelines. We consider several options for refining antitrust enforcement policy. Refinement of enforcement policies is important given the industry restructuring that is likely through health care reform.

Antitrust Laws↗
PubMed1994

Elevated serum levels of a c-erbB-2 oncogene product in ovarian cancer patients and in pregnancy.

Amplification of the proto-oncogene c-erbB-2 (HER-2/neu) has been shown to be a prognostic marker in ovarian cancer. In order to obtain further information on the biological role of the c-erbB-2 gene product p185 it is necessary to quantify expression levels. In this study we evaluated an enzyme-linked immunosorbent assay (ELISA) for the extracellular domain of p185 to determine whether a soluble oncoprotein fragment can be detected in the serum of ovarian cancer patients and in the serum of pregnant women. Sera from 199 women (57 previously untreated ovarian cancer patients, 62 pregnant women and 80 healthy controls) were assayed in a sandwich ELISA utilizing two mouse monoclonal antibodies. To study c-erbB-2 overexpression in ovarian cancer tissue samples we have used an immunohistochemical technique involving a monoclonal antibody specifically reactive with the external domain of the protein p185. The mean serum value for the normal controls was 1203 HNU/ml with a standard deviation (SD) of 279 HNU/ml and a range of 595-1947 HNU/ml. We chose a level of 1761 HNU/ml (2 SD above the mean) as a cut-off to distinguish individuals with elevated levels. The ovarian cancer patients' serum values ranged from 526 to 16,332 HNU/ml. Immunohistochemically detectable p185 was noted in 8 of 57 ovarian cancer patients. The oncoprotein fragment levels in the sera from these 8 patients ranged from 878 to 16,332 HNU/ml. Of 8 patients with p185 overexpression in their tumors, 4 had elevated serum levels. In the sera from the 49 cancer patients without overexpression the values were distributed in the range 526-2892 HNU/ml. There was no association between serum oncoprotein fragment levels and tumor stage, histological type or grading. Serum concentrations of the p185 fragment in pregnancy ranged from 612 to 3265 HNU/ml. The highest levels were found in the third trimester. The results of the present study raise the possibility that the soluble c-erbB-2 protein level in serum is an indicator for cell proliferation and therefore deserves further evaluation as a diagnostic tool in ovarian cancer patients and pregnancy.

Adult↗
PubMed1994

Development of patient satisfaction surveys in the Czech Republic: a new approach to an old theme.

Although patient satisfaction surveys have become well established features of Western healthcare systems, free expression was suppressed for much of the past 50 years in the Czech Republic. As part of a quality assurance program established at the University Hospital Kralovske Vinohrady in Prague, and under the direction of a sociologist, a patient satisfaction pilot study was instituted as a precursor to a broader and ongoing survey. A cohort of 150 patients who were discharged following hospitalization on one of three medical or surgical services were given the opportunity to respond to a 36 item questionnaire devised as a result of study of similar instruments, 101 completed the questionnaire. Patients who responded were comparable to those hospitalized on these services, and other factors, demographic and otherwise, were likewise comparable. Once the concerns regarding the opportunity for free expression were addressed, it was found that interpersonal interactions with physicians, nurses, and other healthcare personnel provided the greatest satisfaction for patients and greatly exceeded amenities such as the quality of the hospital room and food. As a result of this pilot study, a subsequent survey of more than 500 patients has begun. It is believed that such surveys will provide useful data for quality assurance as well as involving patients in an assessment of the care provided.

Cohort Studies↗
PubMed1994

Overexpression of the oncogene c-erb B2 in primary ovarian cancer: evaluation of the prognostic value in a Cox proportional hazards multiple regression.

To date, there are no prognostic factors in ovarian cancer that adequately account for tumor biology and disease behavior. In recent years, some reports have described the prognostic significance of the amplification and overexpression of the oncogene c-erb B2 in various human cancers. Concerning ovarian cancer, this is still a matter of discussion. In the present study, tumor tissue of 275 patients treated for ovarian cancer at the Department of Obstetrics and Gynecology of the University of Göttingen between 1982 and 1992 was immunohistochemically analyzed for overexpression of c-erb B2-encoded transmembrane protein p185. In 19% (51 of 275 cases), p185 overexpression was detected. The percentage of p185-positive cases varied from 7 to 46% according to histological subtype. Correlation with tumor stage and the degree of histological differentiation was not observed. Patients with p185-positive tumors had a significantly worse prognosis (p = 0.001); median survival was 20 months compared with 33 months for p185-negative tumors. In the Cox proportional hazards regression, p185 overexpression was identified as an independent prognostically relevant factor. These results suggest that overexpression of oncogene c-erb B2 in ovarian cancer characterizes a group with unfavorable tumor biology and a significantly worse prognosis.

ErbB Receptors↗