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Biomedical subjects

M Binder

Publications and source records attributed to M Binder.

At least 19 recordsLinked to original sources
PubMed1996

Creatine kinase-mb fraction and cardiac troponin T to diagnose acute myocardial infarction after cardiopulmonary resuscitation.

OBJECTIVES: This study sought to evaluate the diagnostic value of the biochemical markers creatine kinase (CK), creatine kinase-MB fraction (CK-MB) and cardiac troponin T (cTNT) to diagnose acute myocardial infarction (AMI) after cardiopulmonary resuscitation (CPR). BACKGROUND: Elevations of CK and CK-MB after CPR are a frequent finding and might be associated with ischemic myocardial injury, as well as physical trauma to the chest. METHODS: Patients who had cardiac arrest and primary successful resuscitation were included in the study. The diagnosis of AMI was confirmed or ruled out by means of typical electrocardiographic findings, thallium-201 myocardial scintigraphy or autopsy, if death occurred during the hospital period, in 39 primary survivors of sudden cardiac death. In 24 patients (62%) the diagnosis of AMI was established. Serum cTNT, CK and CK-MB were measured, and the CK-MB/CK ratio was calculated on admission and after 12 h. RESULTS: On admission all markers of myocardial injury proved to be weak methods for the diagnosis of AMI. After 12 h cTNT as well as CK-MB exhibited a similar diagnostic performance; CK and the CK-MB/CK ratio proved to be worthless. Sensitivity and specificity for a cTNT cutoff value of 0.6 ng/ml, 12 h after cardiac arrest, were 96% and 80%, respectively. For a CK-MB cutoff value of 26 U/liter, sensitivity was 96% and specificity was 73%. CONCLUSIONS: Cardiac TNT and CK-MB are valuable tools in detecting AMI as the cause of sudden cardiac death. However, there is a considerable lack of sensitivity and specificity. Cardiac injury is probably caused not only by AMI, but also by myocardial damage related to CPR efforts.

Animals↗
PubMed1996

103Pd brachytherapy and external beam irradiation for clinically localized, high-risk prostatic carcinoma.

PURPOSE: To summarize biochemical failure rates and morbidity of external beam irradiation (EBRT) combined with palladium (103Pd) boost for clinically localized high-risk prostate carcinoma. METHODS AND MATERIALS: Seventy-three consecutive patients with stage T2a-T3 prostatic carcinoma were treated from 1991 through 1994. Each patient had at least one of the following risk factors for extracapsular disease extension: Stage T2b or greater (71 patients), Gleason score 7-10 (40 patients), prostate specific antigen (PSA) > 15 (32 patients), or elevated prostatic acid phosphatase (PAP) (17 patients). Patients received 41 Gy EBRT to a limited pelvic field, followed 4 weeks later by a 103Pd boost (prescription dose: 80 Gy). Biochemical failure was defined as a PSA greater than 1.0 ng/ml (normal < 4.0 ng/ml). Patients whose PSA was still decreasing at the last follow-up were censored at that time. Patients whose PSA plateaued at a value greater than 1.0 were scored as failures at the time the PSA first plateaued. RESULTS: The overall, actuarial freedom from biochemical failure at 3 years after treatment was 79%. In Cox proportional hazard multivariate analysis, the strongest predictor of failure was elevated acid phosphatase (p = 0.04), followed by PSA (p = 0.17), Stage (p = 0.23), and Gleason score (p = 0.6). Treatment-related morbidity was usually limited to temporary, RTOG Grade 1-2 urinary symptoms. One patient, who had both a transurethral incision of the prostate (TUIP) and a transurethral resection of the prostate (TURP), developed low-volume urinary incontinence. The actuarial potency rate at 3 years after implantation was 77% for 46 patients who were sexually potent prior to implant. CONCLUSION: Biochemical freedom from failure rates following combined EBRT and 103Pd brachytherapy for clinically localized, high-risk prostate cancer compare favorably with that reported after conventional dose EBRT alone. Morbidity has been acceptable.

Aged↗
PubMed1996

Pip2p: a transcriptional regulator of peroxisome proliferation in the yeast Saccharomyces cerevisiae.

In Saccharomyces cerevisiae, peroxisomes are the exclusive site for the degradation of fatty acids. Upon growth with the fatty acid oleic acid as sole carbon source, not only are the enzymes of beta-oxidation and catalase A induced, but also the peroxisomal compartment as a whole increases in volume and the number of organelles per cell rises. We previously identified a cis-acting DNA sequence [oleate response element (ORE)] involved in induction of genes encoding peroxisomal proteins. The aim of our investigation was to test whether a single mechanism acting via the ORE coordinates the events necessary for the proliferation of an entire organelle. Here we report the cloning and characterization of the oleate-specific transcriptional activator protein Pip2p (pip: peroxisome induction pathway). Pip2p contains a typical Zn(2)-Cys(6) cluster domain and binds to OREs. A pip2 deletion strain is impaired in growth on oleate as sole carbon source and the induction of beta-oxidation enzymes is abolished. Moreover, only a few, small peroxisomes per cell can be detected. These results indicate that fatty acids activate Pip2p, which in turn activates the transcription of genes encoding beta-oxidation components and acts as the crucial activator of peroxisomes.

Amino Acid Sequence↗
PubMed1996

Disruption of the Cbfa2 gene causes necrosis and hemorrhaging in the central nervous system and blocks definitive hematopoiesis.

The CBFA2 (AML1) gene encodes a DNA-binding subunit of the heterodimeric core-binding factor. The CBFA2 gene is disrupted by the (8;21), (3;21), and (12;21) chromosomal translocations associated with leukemias and myelodysplasias in humans. Mice lacking a CBF alpha 2 protein capable of binding DNA die between embryonic days 11.5 and 12.5 due to hemorrhaging in the central nervous system (CNS), at the nerve/CNS interfaces of cranial and spinal nerves, and in somitic/intersomitic regions along the presumptive spinal cord. Hemorrhaging is preceded by symmetric, bilateral necrosis in these regions. Definitive erythropoiesis and myelopoiesis do not occur in Cbfa2-deficient embryos, and disruption of one copy of the Cbfa2 gene significantly reduces the number of progenitors for erythroid and myeloid cells.

Animals↗
PubMed1996

Creatine kinase and creatine kinase-MB release after nontraumatic cardiac arrest.

The aim of the study was to describe the course of serum creatine kinase (CK) and its MB fraction (CK-MB) in patients surviving cardiac arrest, and to identify factors influencing CK and CK-MB release. The study was set in the community of Vienna, Austria. Data concerning cardiopulmonary resuscitation, collected within a period of 33 months, were evaluated retrospectively and compared with laboratory blood investigations collected prospectively (on admission and after 6, 12, and 24 hours) in 107 adult patients surviving a witnessed cardiac arrest for 24 hours. CK and CK-MB were elevated in >75% of the patients within 24 hours. Release of CK and CK-MB was mainly associated with electrocardiographic evidence of acute myocardial infarction (AMI) cumulative energy administered during defibrillation, and duration of chest trauma by compression. The CK-MB/CK ratio was elevated in 32% of the patients. Of patients with electrocardiographic evidence of AMI, only 49% had an elevated CK-MB/CK ratio. In conclusion, the elevation in serum CK and CK-MB fraction in patients after nontraumatic cardiac arrest is a frequent finding, and is associated with ischemic myocardial injury, as well as physical trauma to the chest. This should be considered when interpreting the course of CK and CK-MB fraction for the diagnosis of AMI.

Adult↗
PubMed1996

Impaired hemorheology in patients with postmastectomy lymphedema.

Lymphedema of the arm is one of the most disabling and serious complications of breast cancer. Apart from tumor infiltration or fibrosis of lymphatic pathways, little is known about factors favoring the development of lymphedema. In the present study, we investigated the impact of rheologic parameters, e.g. red cell aggregation (EA) and plasma viscosity (PV), and of capillary morphology and capillary flow in patients with breast cancer with (n = 18) and without (n = 18) lymphedema. Patients with lymphedema showed a significant increase of red cell aggregation (p < 0.001) that indicates a systemic component of lymphedema and might offer a possibility of prevention and therapy of this condition. A hitherto unclassified protein factor favoring red cell aggregation and lymphedema might be postulated.

Aged↗
PubMed1996

Immunogold labeling of yeast cells: an efficient tool for the study of protein targeting and morphological alterations due to overexpression and inactivation of genes.

Immunogold labeling on Lowicryl HM20 resin sections is a valuable complement to biochemical methods as well as methods of molecular biology in the study of basic mechanisms in the yeast system. This contribution presents an overview of the state of the art. Emphasis is put on the explanation of caveats and pitfalls rather than on detailed bench protocols. In the Applications section the morphological aspect of genetic manipulation is accentuated and links to human pathology are indicated. The morphological consequences of genetic manipulations may gain importance in view of the efforts made to establish gene therapies. In particular, the contribution of immunoelectron microscopy to the elucidation of peroxisomal targeting signals and to the detection and identification of morphological alteration due to overexpressed, mutated or deleted genes in the context of peroxisome biogenesis is described.

Animals↗
PubMed1996

Hemodynamic effects of active compression-decompression after prolonged CPR.

BACKGROUND: This study was designed to test the effects of active compression-decompression (ACD) versus standard (STD) cardiopulmonary resuscitation (CPR) on hemodynamics after prolonged cardiac arrest (CA). METHODS AND RESULTS: After nontraumatic prehospital CA, 21 patients were resuscitated in a prospective nonblinded setting sequentially with STD and ACD CPR at the emergency department, if it had not been possible to achieve restoration of spontaneous circulation (ROSC) before admission. The compression rate was 80/min with a 50% duty cycle, and 1 mg epinephrine was given every 5th min. Invasive arterial, central venous pressure and end tidal CO2 (ETCO2) were monitored. Comparing coronary perfusion pressure (CoPP) and ETCO2, no significant differences between STD and ACD CPR were found. In 3 cases ROSC could be achieved for a short time. CONCLUSIONS: In our study, a comparison of STD and ACD CPR revealed no significant differences in coronary perfusion pressures and ETCO2. We conclude that after prolonged CA, ACD CPR does not provide an apparent hemodynamic advantage over STD CPR.

Aged↗
PubMed1996

Accuracy and reliability of noninvasive continuous finger blood pressure measurement in critically ill patients.

OBJECTIVE: To evaluate the accuracy and reliability of noninvasive continuous finger blood pressure measurement in critically ill patients. DESIGN: Prospective data collection. SETTING: Emergency department in a 2,000-bed hospital. PATIENTS: Thirty-nine patients admitted to the emergency department requiring invasive arterial blood pressure monitoring were enrolled to the study protocol. INTERVENTIONS: Continuous noninvasive blood pressure measurement was performed on the middle phalanx of the second and third finger, using a test instrument which provides continuous arterial waveform display with the use of a finger cuff. Invasive mean arterial blood pressure measurement was done by cannulation of the radial artery and direct transduction of the systemic arterial pressure waveform. MEASUREMENTS AND MAIN RESULTS: Three thousand one hundred eighteen pairs of simultaneous finger cuff and intra-arterial blood pressure measurements were collected in 1-min intervals from 39 patients over a total of 51.8 hrs. The overall discrepancy between both measurements was 0.10 mm Hg. The standard deviation of the differences was +/- 5.02 mm Hg. The mean bias in patients treated with catecholamines was 0.01 mm Hg and was not different from the bias observed in patients without catecholamines (mean bias: 0.23 mm Hg; p > .22). Whereas 95% of all comparisons between finger cuff and intra-arterial measurement had a discrepancy < or = +/- 10 mm Hg, 4.7% had a discrepancy between +/- 10.1 to 15 mm Hg and 0.3% exhibited a discrepancy > +/- 15 mm Hg. In 29 (74%) patients, the duration of errors > 10 mm Hg was < or = 1 min. In seven (18%) patients, the duration of errors > 10 mm Hg was between 2 to 3 mins and in three (8%) patients, the errors lasted for > 3 mins. CONCLUSIONS: Our data provide a guide to the accuracy and reliability of noninvasive finger blood pressure measurements in critically ill patients. Although most test instrument measurements were reliable, in 8% of all patients large discrepancies (> 10 mm Hg) between both measurements with a duration of > 3 mins were noted. Concerning the considerable risk for arterial cannulation, our preliminary data demonstrate that the test instrument (PORTAPRES, TNO Biomedical Instrumentation Research Unit; The Netherlands) is an advance in noninvasive monitoring of critically ill patients and may be useful in most emergency clinical settings.

Adult↗
PubMed1996

Obsessive-compulsive characteristics: from symptoms to syndrome.

OBJECTIVE: To assess the distribution and severity of obsessions and compulsions in a nonclinical adolescent population. METHOD: During preinduction military screening, 861 sixteen-year-old Israelis completed a questionnaire regarding the lifetime presence of eight obsessive-compulsive (OC) symptoms and three severity measures. The presence or absence of obsessive-compulsive disorder (OCD) or subclinical OCD was ascertained by an independent interview. RESULTS: Although only 8.0% and 6.3% of respondents reported disturbing and intrusive thoughts, respectively, 27% to 72% of subjects endorsed the six remaining OCD symptoms. Twenty percent of subjects regarded the symptoms they endorsed as senseless and 3.5% found them disturbing; 8% reported spending more than an hour daily on symptoms. OCD and subclinical OCD cases differed significantly from non-OCD cases, but not from each other, in distress and mean number of symptoms. Although the distribution of nine of the items differed for noncases, compared with OCD and subclinical OCD cases, the distributions for all items overlapped markedly across the three groups. CONCLUSIONS: OC phenomena appear to be on a continuum with few symptoms and minimal severity at one end and many symptoms and severe impairment on the other. Defining optimal cutoff points for distinguishing between psychiatric disorder and OC phenomena that are common in the general population remains an open question.

Adolescent↗
PubMed1996

Limitations of high frequency ultrasound in determining the invasiveness of cutaneous malignant melanoma.

Preoperative assessment of melanoma invasion by sonometry has been reported to exhibit a high correlation with postoperative histometry based on the determination of a regression coefficient. We believe that this approach is not adequate and that it can be misleading. We therefore applied an appropriate statistical approach to our data to re-examine this issue. Preoperative measurements by sonometry were compared with postoperative histometry in 71 consecutive patients with the clinical diagnosis of malignant melanoma. Patients with the histological diagnosis of melanoma in situ (n = 13) were excluded from this comparison, as sonometry cannot distinguish structures restricted to the epidermis and Breslow thickness is not routinely determined in Clark level I melanomas. The agreement between sonometry and histometry was analysed by plotting the mean of the two methods against their difference. By linear regression analysis the correlation coefficient (r) in the invasive melanomas (n = 58) was found to be 0.92. The median thickness of the invasive tumours by sonometry was 1.36 mm, and by histometry 0.89 mm. In 95% of the cases sonometry differed by 37% above to 48% below the values obtained by histometry. Thus, we conclude that the accuracy of sonometry in predicting preoperative tumour thickness- and tumour invasiveness-is far lower than previously reported.

Adult↗
PubMed1996

Increased nuclear volume in metastasizing "thick" melanomas.

Tumor invasion is the most reliable prognostic factor for primary stage I melanoma. "Thick" melanomas, with a Breslow thickness of more than 4 mm, tend to have a poor prognosis. Exceptions occur: some patients have no further recurrence of tumor. In an attempt to determine prognostic markers for "thick" clinical stage I melanomas, we investigated the volume-weighted mean nuclear volume of primary melanomas with tumor invasions > or = 4.0 mm in 32 patients. Seventeen of these patients developed melanoma metastases within a follow-up period of 60 mo; 15 patients who did not developed metastases and were comparable with regard to clinical and histological criteria were selected as a comparison group. Volume-weighted mean nuclear volume (Vv) is determined by a technique that permits an unbiased, efficient, shape- and orientation-independent, 3-dimensional estimation of nuclear size in tissues. This technique has been employed successfully in the prognostic assessment of stage I and II melanomas and was recently proven to be a sensitive marker for thin, high-risk melanomas. In our patients, Vv was determined by computer-assisted image analysis on Feulgen-stained sections by stereologic estimation of the Vv. The mean Vv (+/-SD) of primary melanomas with subsequent metastatic course was 794.99 +/- 209.18 micron3 (range: 409.48-1161.9 micron3), whereas primary melanoma lesions without subsequent metastases exhibited a mean Vv 640.54 +/- 205.07 micron3 (range: 206.7-927.48 micron3). This difference was found to be statistically significant (p = 0.0439). "Thick" melanomas with subsequent metastases thus exhibited a significantly higher Vv than did melanomas that did not metastasize.

Adult↗
PubMed1996

Treatment of skin aging with topical estrogens.

BACKGROUND: The coincidence of climacteric symptoms and the beginning of skin aging suggests that estrogen deficiency may be a common and important factor in the perimenopausal woman. Often hormones have been considered important in endogenous aging of the skin, but their role has not been clearly defined. Therefore, we investigated, whether topical treatment of the skin with estrogen could reverse some of the changes in the aging skin. MATERIAL AND METHODS: The effects of 0.01% estradiol and 0.3% estriol compounds were compared in 59 preclimacteric women with skim aging symptoms. Monthly determinations of estrodiol (E2), follicle-stimulating hormone (FSH), and prolactin (PRL) were done and the monthly clinical monitoring was supplemented by measurements of skin hydration by corneometry and profilometry. In 10 patients, skin biopsies were taken for immunohistochemical determination of collagen types I and III. RESULTS: After treatment for 6 months, elasticity and firmness of the skin had markedly improved and the wrinkle depth and pore sizes had decreased by 61 to 100% in both groups. Furthermore, skin moisture had increased and the measurement of wrinkles using skin profilometry, revealed significant, or even highly significant, decreases of wrinkle depth in the estradiol and the estriol groups, respectively. On immunohistochemistry, significant increases of Type III collagen labeling were combined with increased numbers of collagen fibers at the end of the treatment period. As to hormone levels, only those of PRL had increased significantly and no systemic hormonal side effects were noted.

Administration, Topical↗
PubMed1996

Arterial blood pressure after human cardiac arrest and neurological recovery.

BACKGROUND AND PURPOSE: In animal cardiac arrest studies, outcome has been improved by inducing arterial hypertension early after return of spontaneous circulation. The aim of our study was to evaluate whether arterial blood pressure within the first minutes and hours after return of spontaneous circulation influences neurological recovery in human cardiac arrest survivors. METHODS: Of 136 retrospectively evaluated patients after sudden cardiac death, two groups were defined: group 1, mean arterial blood pressure (MABP) within 5 minutes after return of spontaneous circulation above 100 mm Hg; group 2, MABP of 100 mm Hg or less. Thereafter MABP was measured every 5 minutes until 2 hours after return of spontaneous circulation. The groups were compared in regard to age, sex, in/out of hospital, witnessed/not witnessed, first electrocardiographic rhythm, time from cardiac arrest to beginning of life support and to return of spontaneous circulation, cumulative epinephrine dose administered, and best neurological outcome within 6 months. RESULTS: In group 1 (n = 54) good neurological recovery was observed in 63% and in group 2 (n = 82) in 55% (chi 2 = 0.87, P = NS). Both groups exhibited comparable baseline values except that time intervals from beginning of life support to return of spontaneous circulation were shorter in group 1. After we controlled for this difference with Spearman's partial rank correlation (rs), there was no association between MABP measured within the first 5 minutes and outcome (rs = -.023; P = NS). Good neurological recovery was independently and directly related to MABP measured during 2 hours after return of spontaneous circulation (rs = .26; P < .01). CONCLUSIONS: In human cardiac arrest survivors, good functional neurological recovery was independently and positively associated with arterial blood pressure during the first 2 hours after human cardiac arrest but not with hypertensive reperfusion within the first minutes after return of spontaneous circulation.

Aged↗
PubMed1996

Intracellular distribution of ibuprofen within monocytes.

The interaction of ibuprofen (CAS 15687-27-1) with muscle proteins was investigated in vitro and binding to actin was found to be more marked than to other muscle proteins. Actin polymerization, however, was not influenced by this interaction. The kinetics of ibuprofen internalization by human monocytes/macrophages from peripheral blood at 37 degrees C and its partitioning to different cellular compartments was studied and compared to the actin content of these subcellular fractions. The bulk of cell-bound ibuprofen (89.7%) was found in the cell debris fraction (1,000 g sediment), 7.3% were recovered in the 10,000 g sediment, only 0.5% in the 100,000 g sediment and 2.5% in the cytosolic fraction. The distribution of F-actin to the different subcellular fractions was verified by fluorescence analysis using NBD-phallacidin. Four times more F-actin was found in the 1,000 g sediment than in the 10,000 g fraction, while the microsomal fraction contained only 8% of total F-actin. In the cytosol, significant amounts of soluble actin were detected. These data indicate that ibuprofen could theoretically interact with actin in all the cellular subfractions to which it is distributed after internalization.

Actins↗
PubMed1995

A C-terminal region of the Saccharomyces cerevisiae transcription factor ADR1 plays an important role in the regulation of peroxisome proliferation by fatty acids.

The Saccharomyces cerevisiae transcriptional activator ADR1, which controls ADH2 gene expression, was shown to be involved in the regulation of peroxisome proliferation. To study the mode of action of ADR1, we compared strains carrying the adr1-1 mutation, high or low copy numbers of the ADR1 gene, the constitutive allele ADR1-5c, and 3'-deletions of ADR1. High ADR1 gene dosage increased the transcription of genes encoding peroxisomal proteins as compared to one copy of the ADR1 gene. Furthermore, overexpression of ADR1 under ethanol growth conditions induced the proliferation of peroxisomal structures. The organelles were observed to be localized in clusters, a typical feature of peroxisomes induced by oleic acid. In contrast, the ADR1-5c allele, which induces ADH2 expression to a level comparable to that of high ADR1 gene dosage was found to have only a small effect. An analysis of functional domains of the ADR1 protein revealed that the N-terminal 220 amino acids of ADR1 were sufficient for wild-type levels of transcription of the FOX2, FOX3, and PAS1 genes, but the entire ADR1 protein was required for complete induction of the CTA1 gene and for growth oleic acid medium. Our data suggest that a functional domain of the ADR1 protein localized between residues 643 and 1323 is required for the induction of peroxisomal structures and for the utilization of oleic acid.

ATPases Associated with Diverse Cellular Activitie↗
PubMed1995

Clinical evaluation of different doses of intravenous enalaprilat in patients with hypertensive crises.

BACKGROUND: The appropriate dose of intravenous enalaprilat to be used in the treatment of hypertensive crisis is controversial. There has been no comparative study of the efficacy and safety of different dosages of enalaprilat in hypertensive patients. METHODS: Sixty-five consecutive patients with hypertensive urgencies (systolic blood pressure > 210 mm Hg and/or diastolic blood pressure > 110 mm Hg) or emergencies (diastolic blood pressure > 100 mm Hg and evidence of end-organ damage, ie, angina pectoris, hypertensive encephalopathy, or congestive heart failure) admitted to an emergency department from January 1, 1994, to September 30, 1994, were identified. The patients were randomized to receive different doses of enalaprilat (0.625, 1.25, 2.5, and 5 mg). Response to treatment was defined as a stable reduction of systolic blood pressure to below 180 mm Hg and diastolic blood pressure to below 95 mm Hg within 45 minutes after the start of treatment and relief of symptoms in patients with hypertensive emergencies. RESULTS: In 41 (63%) of 65 patients, the treatment goal was reached. Twenty-four patients (37%) failed to achieve the goal of treatment within 45 minutes after administration of enalaprilat. The response rates in the 0.625-mg, 1.25-mg, 2.5-mg, and 5-mg groups were 67%, 65%, 59%, and 62%, respectively. The proportion of patients initially randomized who responded to treatment was not different between any of the four groups of enalaprilat doses. There were no significant differences according to enalaprilat dose with respect to changes in systolic, diastolic, and mean arterial blood pressure. No severe side effects were observed. CONCLUSION: Enalaprilat is a safe antihypertensive drug with moderate efficacy in the treatment of hypertensive crisis. As doses above 0.625 mg alter neither response rates nor the magnitude of blood pressure reduction, we recommend 0.625 mg as the initial dose in the treatment of hypertensive crisis.

Aged↗