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Biomedical subjects

L Frey

Publications and source records attributed to L Frey.

At least 19 recordsLinked to original sources
PubMed2001

Practical asymmetric synthesis of a selective endothelin A receptor (ETA) antagonist.

[structure: see text]. A practical, chromotography-free asymmetric synthesis was developed for the large scale preparation of an endothelin receptor antagonist 2. This synthesis includes a new efficient process for the preparation of 6-bromo-2,3-dihydrobenzofuran, a stereoselective conjugate addition of an aryllithium followed by stereospecific addition of the Grignard reagent of the top aryl bromide, and an aminophosphate-mediated sterospecific intramolecular enolate alkylation, which led to the formation of the five-membered ring bearing three contiguous asymmetric centers.

Antihypertensive Agents↗
PubMed2001

Prevention of secondary health conditions in adults with developmental disabilities: a review of the literature.

PURPOSE: To compile empirical findings regarding prevention strategies for secondary conditions experienced by adults with developmental disabilities. METHOD: The PsycLit and PubMed databases were searched for articles addressing the 20 most pervasive secondary conditions and the prevention of secondary conditions in general. RESULTS: Of more than 2000 articles examined, 25 met criteria for inclusion. None could be categorized as a primary approach to prevention, 19 involved secondary and six involved tertiary approaches. The majority included between one and ten participants. Nine studies involved the administration of treatment, three providing certain experiences, two chart review, and 11 a training approach. Injuries due to self-abuse, communication problems, dental hygiene problems, and problems with memory, persistence and mobility were addressed. CONCLUSION: Little is known regarding the prevention of secondary conditions within this population. The authors stress the necessity to focus research efforts on greater understanding of the linkage between disability, rehabilitation and public health models.

Adolescent↗
PubMed2001

Intensive care after minimally invasive and conventional coronary surgery: a prospective comparison.

OBJECTIVE: The purpose of this study was to compare the intensive care course of patients after minimally invasive coronary surgery to conventional coronary artery bypass grafting. DESIGN: Prospective observational study. SETTING: Intensive care unit of a university hospital. PATIENTS AND PARTICIPANTS: One hundred and five patients with two-vessel disease consecutively scheduled for elective coronary bypass surgery were enrolled. INTERVENTIONS: Two techniques of revascularization were performed: the Octopus procedure via median sternotomy without cardiopulmonary bypass (n = 52) and conventional coronary artery bypass grafting CABG (n = 53). MEASUREMENTS AND RESULTS: Three major categories describing the patients' postoperative course were defined: (1) clinical and laboratory findings, i.e., transfusion rate, catecholamine support, duration of ventilation, Simplified Acute Physiology Score II (SAPS II), serum levels of cardiac enzymes and lactic acid; (2) postoperative complications, i.e., incidence of myocardial infarction (MI), atrial fibrillation (AF), and neurological deficits; (3) this category was defined as "the extent of care" as represented by the Therapeutic Intervention Scoring System (TISS), and the length of stay in the ICU and in the hospital. In the Octopus group significantly lower figures were noted for duration of ventilation [6.1(5.5/9.5) vs 10.2(8.2/11.8) h], cardiac enzymes (CK-MB-Mass [5.1(2.0/8.3) vs 31.3(21.4/39.3) ng/ml], and lactic acid [2.0(1.5/3.3) vs 3.2(2.2/6.5) mmol/l]), incidence of AF (2/52 vs 9/53), and neurological deficits (0/52 vs 4/53), TISS score [72(44/83) vs 84(73/93)], LOS in the ICU [2(1/2) vs 2(2/2) days], and in the hospital [6(5/9) vs 9(8/12) days]. Catecholamine support, SAPS II scores, and incidence of MI of each group did not differ significantly. CONCLUSIONS: Off-pump coronary surgery via the Octopus technique was superior to conventional CABG regarding the course of patients in the early postoperative period. This implies benefits for the patients and the entire healthcare system.

APACHE↗
PubMed2001

High-resolution constant-height imaging with apertured silicon cantilever probes.

We present high-resolution aperture probes based on non-contact silicon atomic force microscopy (AFM) cantilevers for simultaneous AFM and near-infrared scanning near-field optical microscopy (SNOM). For use in near-field optical microscopy, conventional AFM cantilevers are modified by covering their tip side with an opaque aluminium layer. To fabricate an aperture, this metal layer is opened at the end of the polyhedral probe using focused ion beams (FIB). Here we show that apertures of less than 50 nm can be obtained using this technique, which actually yield a resolution of about 50 nm, corresponding to lambda/20 at the wavelength used. To exclude artefacts induced by distance control, we work in constant-height mode. Our attention is particularly focused on the distance dependence of resolution and to the influence of slight cantilever bending on the optical images when scanning at such low scan heights, where first small attractive forces exerted on the cantilever become detectable.

Journal Article↗
PubMed2001

[New platelet inhibitors].

The antiplatelet action of acetylsalicylic acid is mostly used in vascular medicine. In the meantime two other classes of platelet inhibiting agents have been introduced. Thieopyridines (Ticlyridin, Clopidogrel) have been shown to inhibit ADP induced platelet aggregation with persistence of this effect for several days after withdrawal. The short acting intravenous Glycoprotein IIb/IIIa inhibitors considerably improved the management of acute coronacy syndrome. The above mentioned compounds may be applied in combination at least for some days, and heparins are given in addition. Mainly the bleeding complications are to be taken into account especially if patients have to undergo emergency interventions. Hemodialysis or platelet concentrates are recommended to antagonise the antiplatelet effects immediately.

Anesthesia↗
PubMed2000

[Significance of perfusion of the gastrointestinal tract in shock].

The splanchnic perfusion is reduced early in the course of any shock. The mucosa of the gut suffers most as it experiences a high oxygen demand even in the steady state. The specific arrangement of the micro vessels within the villus of the mucosa exposes the tip of the villus at the highest risk for ischemia, particularly in low flow states. As a consequence the integrity of the mucosal layer is compromised and dysfunction of the mucosal barrier may allow bacteria and toxins to translocate from the gut lumen. Activation of leukocytes and stimulation of cytokine synthesis may comprise a sustained inflammatory response syndrome. So far there is a good body of evidence that the splanchnic region may play an important role in the pathophysiological sequence from shock to organ dysfunction.

Animals↗
PubMed2000

Markers of myocardial ischemia after minimally invasive and conventional coronary operation.

BACKGROUND: The purpose of this study was to evaluate the course of serum markers of myocardial tissue damage after two different types of minimally invasive coronary surgical procedures (MICS) as compared with conventional coronary artery bypass grafting (CABG). METHODS: We enrolled 87 patients with one- or two-vessel disease scheduled for one of the three procedures: minimally invasive direct coronary artery bypass grafting (MIDCABG) by lateral thoracotomy (n = 29), the OCTOPUS method by median sternotomy (n = 27), and CABG (n = 31). Creatine kinase activity (CK), creatine kinase MB activity (CK-MB act), creatine kinase MB mass concentration (CK-MB mass), myoglobin concentration (MG), and cardiac troponin I concentration (cTnI) were measured perioperatively until the second postoperative day. RESULTS: Creatine kinase-MB, CK-MB mass, and cTnI were significantly higher after CABG and were nearly maintained within the normal range in MICS. Creatine kinase and MG were significantly lower in the OCTOPUS group than in the MIDCABG or CABG groups. CONCLUSIONS: Minimally invasive coronary surgical procedures cause less myocardial injury than CABG as indicated by specific serum markers. However, higher CK and MG reflect more substantial skeletal muscle trauma during MIDCABG operation compared with OCTOPUS procedures.

Adult↗
PubMed2000

Intermittent atrial level right-to-left shunt with temporary hypoxemia in a patient during support with a left ventricular assist device.

We report a 56-year-old male patient developing hypoxemia after surgical replacement of infected valves of a left ventricular assist device (LVAD, Novacor) which had supported him during the previous 15 months. Contrast transesophageal echocardiography (TEE) revealed an atrial septal defect with intermittent right-to-left shunt across a patent foramen ovale. We postulate that the shunt detected in this patient occurred as a consequence of reduced pulmonary vascular compliance due to positive end-expiratory pressure (PEEP) and an increase of mean intrathoracic pressure. Furthermore, we hypothesize that synchronized LVAD operation exacerbates any potential right-to-left shunt due to the profound left ventricular unloading which occurs during LVAD support. In this first report of a right-to-left shunt from a previously unrecognized patent foramen ovale in a Novacor patient, the subsequent transient hypoxemia could be managed by avoiding PEEP of more than 3 mmHg, and mean airway pressure of more than 11 mmHg and by careful volume replacement in order to prevent the pump from completely emptying the left ventricle (LV) and the left atrium (LA). Thus, prior to every LVAD implantation a transesophageal contrast echocardiography with Valsalva maneuver should be performed to identify intracardiac right-to-left shunt.

Heart Septal Defects, Atrial↗
PubMed1999

Effects of noninvasive positive pressure ventilatory support in non-COPD patients with acute respiratory insufficiency after early extubation.

OBJECTIVE: To investigate the effects of noninvasive positive pressure ventilation (NPPV) on pulmonary gas exchange, breathing pattern, intrapulmonary shunt fraction, oxygen consumption, and resting energy expenditure in patients with persistent acute respiratory failure but without chronic obstructive pulmonary disease (COPD) after early extubation. DESIGN: Prospective study. SETTING: Multidisciplinary intensive care unit of a university hospital. PATIENTS: 15 patients after prolonged mechanical ventilation (> 72 h) with acute respiratory insufficiency after early extubation. INTERVENTIONS: Criteria for early extubation were arterial oxygen tension (PaO2) > or = 40 mm Hg (fractional inspired oxygen 0.21), arterial carbon dioxide tension (PaCO2) < or = 55 mm Hg, pH > 7.32, respiratory rate < or = 40 breaths per min, tidal volume (VT) > or = 3 ml/kg, rapid shallow breathing index < or = 190 and negative inspiratory force > or = 20 cmH2O. After extubation, two modes of NPPV were applied [continuous positive airway pressure (CPAP) of 5 cmH2O and pressure support ventilation (PSV) with 15 cmH2O pressure support]. MEASUREMENTS AND MAIN RESULTS: Oxygenation and ventilatory parameters improved during both modes of NPPV (p < 0.05): increase in PaO2 of 11 mm Hg during CPAP and 21 mm Hg during PSV; decrease in intrapulmonary shunt fraction of 7% during CPAP and 12% during PSV; increase in tidal volume of 1 ml/kg during CPAP and 4 ml/kg during PSV; decrease in respiratory rate 6 breaths/min during CPAP and 9 breaths/min during PSV. Oxygen consumption (15% during CPAP, 22% during PSV) and resting energy expenditure (12% during CPAP, 20% during PSV) were reduced (p < 0.05). PaCO2 decreased, whereas minute ventilation and pH increased during PSV (p < 0.05). The median duration of NPPV was 2 days. Two patients had to be reintubated. CONCLUSIONS: In non-COPD patients with persistent acute respiratory failure after early extubation, NPPV improved pulmonary gas exchange and breathing pattern, decreased intrapulmonary shunt fraction, and reduced the work of breathing.

APACHE↗
PubMed1998

Procalcitonin as a marker of systemic inflammation after conventional or minimally invasive coronary artery bypass grafting.

Cardiac surgery using cardiopulmonary bypass (CPB) often induces a systemic inflammatory response syndrome (SIRS). The concept of minimally invasive direct coronary artery bypass (MIDCAB) eliminates cardiopulmonary bypass. We evaluated the perioperative time course of procalcitonin (PCT) to compare the inflammatory response due to these two different surgical procedures. 57 patients were studied: CABG with CPB (n = 30), MIDCAB without CPB (n = 27). The following data were measured preoperatively, after induction of anesthesia, after separation from CPB in the CABG group or after left internal mammary artery (LIMA)-to-left anterior descending artery (LAD) anastomosis in MIDCAB group, and every 3 hours for the first 42 hours in the ICU: PCT, C-reactive protein (CRP), body temperature, hemodynamic parameters, and the need for catecholamines. Leucocyte counts were measured daily. For statistical analyses the Friedmann, Wilcoxon, or Mann-Whitney U tests were used. PCT in the CABG group rose to a maximum of 2.0 ng/ml (median) at 15 hrs postoperatively. In the MIDCAB group maximal PCT concentration was 0.7ng/ml (median) (p < 0.05). CRP was elevated to 17.1 mg/dl in the CABG and 18.5mg/dl in the MIDCAB group (n.s.). The leucocyte counts were increased on day 2 in the CABG group (p < 0.05). In the CABG group about 25% of the patients needed noradrenaline, but in the MIDCAB group none (p < 0.05). Body temperature did not differ between both groups. The increase in PCT concentration was more pronounced after CABG, indicating a reduced inflammatory response after MIDCAB. CRP was increased after both procedures. PCT reflects the inflammatory response after cardiac bypass surgery with or without CPB.

Aged↗
PubMed1997

[Small-volume resuscitation for hypovolemic shock. Concept, experimental and clinical results].

The concept of small-volume resuscitation, the rapid infusion of a small volume (4 ml/kg BW) of hyperosmolar 7.2-7.5% saline solution for the initial therapy of severe hypovolemia and shock was advocated more than a decade ago. Numerous publications have established that hyperosmolar saline solution can restore arterial blood pressure, cardiac index and oxygen delivery as well as organ perfusion to pre-shock values. Most prehospital studies failed to yield conclusive results with respect to a reduction in overall mortality. A meta-analysis of preclinical studies from North and South America, however, has indicated an increase in survival rate by 5.1% following small-volume resuscitation when compared to standard of care. Moreover, small-volume resuscitation appears to be of specific impact in patients suffering from head injuries with increased ICP and in severest trauma requiring immediate surgical intervention. Results from clinical trials in Austria, Germany and France have demonstrated positive effects of hyperosmolar saline solutions when used for fluid loading or fluid substitution in cardiac bypass and in aortic aneurysm surgery, respectively. A less positive perioperative fluid balance, a better hemodynamic stability and improved pulmonary function were reported. In septic patients oxygen consumption could significantly be augmented. The most important mechanism of action of small-volume resuscitation is the mobilisation of endogenous fluid primarily from oedematous endothelial cells, by which the rectification of shock-narrowed capillaries and the restoration of nutritional blood, flow is efficiently promoted. Moreover, after ischemia reperfusion a reduction in sticking and rolling leukocytes have been found following hyperosmolar saline infusion. Both may be of paramount importance in the long-term preservation of organ function following hypovolemic shock. An increased myocardial contractility in addition to the fluid loading effects of hyperosmolar saline solutions has been suggested as a mechanism of action. This, however, could not be confirmed by pre-load independent measures of myocardial contractility. Some concerns have been raised regarding the use of hyperosmolar saline solutions in patients with a reduced cardiac reserve. A slower speed of infusion and adequate monitoring is recommended for high risk patients. Recently, hyperosmolar saline solutions in combination with artificial oxygen carriers have been proposed to increase tissue oxygen delivery through enhanced O2 content. This interesting perspective, however, requires further studies to confirm the potential indications for such solutions. Many hyperosmolar saline colloid solutions have been investigated in the past years, from which 7.2-7.5% sodium chloride in combination with either 6-10% dextran 60/70 or 6-10% hydroxyethyl starch 200,000 appear to yield the best benefit-risk ratio. This has led to the registration of the solutions in South America, Austria, The Czech Republic, and is soon awaited for North America.

Dextrans↗
PubMed1997

Global tissue oxygenation during normovolaemic haemodilution in young children.

Sixteen patients (1-8 years) scheduled for major general surgery were chosen for the study. They were divided into two groups according to the replacement solution used for haemodilution (HD); whether 6% middle molecular weight hydroxyethyl starch (HES) or 6% dextran 60 (DEX). After induction of general anaesthesia and pulmonary artery catheterization, a precalculated amount of autologous blood was withdrawn while the patient's autologous blood was simultaneously replaced by either HES or DEX. Autologous blood was retransfused at a minimum haematocrit (Hct.) of 17% or at the end of surgery. The following parameters were measured and/or calculated before and after HD, every 20 min intraoperatively and hourly for 6 h postoperatively: heart rate (HR), mean arterial pressure (MAP), Cardiac index (CI), Hct., arterial and mixed venous oxygen content (CaO2, CvO2) and arterio-venous difference of oxygen content (avDO2), oxygen delivery index (DO2I), oxygen consumption index (VO2I). The cardiovascular system remained stable. There was no significant difference as regards SvO2, despite a significant decrease in CaO2 to 10.8 and 10.0 ml.dl-1 (median values) due to reduction of haemoglobin concentration in the HES and DEX groups respectively. In spite of the low hct. values during surgery DO2I remained in normal range (median value 602 and 710 ml.min-1.m-2) in HEX and DEX group respectively. There was no significant change in VO2I after haemodilution (median value 212 and 243 ml.min-1.m-2) in either group. No statistically significant difference was noticed between either groups regarding: CaO2, CvO2, DO2I, VO2I, and no side effects of the colloids were observed. Isovolaemic haemodilution (Hct. approximately 17%) is well tolerated by young children undergoing major elective surgery; global tissue oxygenation was preserved throughout the procedure and both solutions used for haemodilution were equally effective.

Anesthesia, General↗
PubMed1997

Effect of hypertonic saline/dextran on post-stenotic myocardial perfusion, metabolism, and function during resuscitation from hemorrhagic shock in anesthetized pigs.

Resuscitation using small volumes of hypertonic saline solutions normalizes cardiac output without fully restoring arterial pressure. This study compared the efficacy of either 7.2% saline/10% dextran 60 (HSDex) or the identical sodium load of normal saline (NS) to improve regional myocardial blood flow (MBF), contractile function, and oxygen metabolism in the presence of a critical coronary stenosis. Fourteen anesthetized, open-chest pigs (25 +/- 3.6 kg) were instrumented to assess left anterior descending coronary artery (LAD) flow, post-stenotic oxygen, and lactate metabolism, regional myocardial segment shortening (SS, sonomicrometry), and MBF (radioactive microspheres). After implementation of a critical LAD-stenosis, shock was induced by hemorrhage (mean arterial pressure (MAP) 45-50 mmHg for 75 min). Resuscitation was started by infusion (2 min) of either HSDex (n = 7,10% of blood loss) or NS (n = 7, 80% of blood loss); 30 min later 6% dextran 60 (10% of blood loss) was administered in both groups. The LAD-stenosis did not affect myocardial metabolism, SS, or MBF at rest. After hemorrhage, MBF remained unchanged from baseline in non-stenotic but decreased by 53% in post-stenotic myocardium (p < .05). The endo-epicardial flow ratio fell below 1.0 in both areas. SS decreased by 10-15% only in post-stenotic myocardium (p < .05). Resuscitation with both HSDex and NS restored cardiac index (CI) but not MAP. MBF increased above baseline values with either solution in non-stenotic while it remained at shock levels in post-stenotic myocardium, where ischemia persisted as evidenced by lactate production and depressed SS. Neither in non-stenotic nor in post-stenotic myocardium was the epi-endocardial flow ratio normalized upon resuscitation with HSDex or NS. We conclude that in the presence of a flow-limiting coronary stenosis, initial fluid resuscitation with both HSDex and the identical sodium load of NS failed to restore perfusion pressure, redistributed MBF in favor of normally perfused myocardium, and did not reverse ischemia in post-stenotic myocardium.

Animals↗
PubMed1997

Arginine biosynthesis and regulation in Lactobacillus plantarum: the carA gene and the argCJBDF cluster are divergently transcribed.

A cluster of citrulline biosynthetic genes has been cloned and sequenced from a fragment of Lactobacillus plantarum CCM 1904 (ATCC 8014) DNA isolated as complementing a Bacillus subtilis argF mutation. The gene order was carA-argCJBDF, with carA transcribed divergently from the arg cluster. Although other gram-positive bacteria show similar arg clusters, this arrangement for carA is thus far unprecedented. Downstream from the arg cluster, two open reading frames (ORF7 and ORF8) having unknown functions were found. Sequence analysis of the end of a 10.5-kb cloned DNA fragment showed that argF was 3.5 kb from the ldhL gene coding for L-(+)-lactate dehydrogenase. A tree representation of amino acid sequence clustering relationships of 31 ornithine carbamoyltransferases (OTCases) from various organisms revealed two prokaryotic groups: one with ArgF of L. plantarum and one with ArgF of B. subtilis, which are paralogous. This divergence was not observed in vivo because an L. plantarum argF mutant (AM 1215) harboring no OTCase activity was complemented by the argF genes of L. plantarum and B. subtilis. No OTCase activity was detectable when L. plantarum was grown in the presence of saturating amounts of arginine or citrulline. Arginine may repress the citrulline biosynthetic genes in L. plantarum by using 11 identified DNA motifs which resemble the Escherichia coli ARG box consensus and which are in most cases separated by multiples of 11 bp, corresponding to a DNA helical turn. The carA and argCJBDF genes are divergently transcribed. Their putative promoters are 6 bp apart and are partially overlapped by putative ARG boxes, suggesting concerted transcription regulation.

Arginine↗