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Biomedical subjects

J Meyer

Publications and source records attributed to J Meyer.

At least 631 records · Page 35Linked to original sources

Primary structure of hydrogenase I from Clostridium pasteurianum.

Peptides obtained by cleavage of Clostridium pasteurianum hydrogenase I have been sequenced. The data allowed design of oligonucleotide probes which were used to clone a 2310-bp Sau3A fragment containing the hydrogenase encoding gene. The latter has been sequenced and was found to translate into a protein composed of 574 amino acids (Mr = 63,836), including 22 cysteines. C. pasteurianum hydrogenase is homologous to, but longer than, the large subunit of Desulfovibrio vulgaris (Hildenborough) [Fe] hydrogenase. It includes an additional N-terminal domain of ca. 110 amino acids which contains eight cysteine residues and which therefore could accommodate two of its postulated four [4Fe-4S] clusters. C. pasteurianum hydrogenase is most similar in length, cysteine positions, and sequence altogether to the translation product of a putative hydrogenase encoding gene from D. vulgaris (Hildenborough). Comparisons of the available [Fe] hydrogenase sequences show that these enzymes constitute a structurally rather homogeneous family. While they differ in the length of their N-termini and in the number of their [4Fe-4S] clusters, they are highly similar in their C-terminal halves, which are postulated to harbor the hydrogen-activating H cluster. Five conserved cysteine residues occurring in this domain are likely ligands of the H cluster. Possible ligation by other residues, and in particular by methionine, is discussed. The comparisons carried out here show that the H clusters most probably possess a common structural framework in all [Fe] hydrogenases. On the basis of the available data on these proteins and on the current developments in iron-sulfur chemistry, the H clusters possibly contain six to eight iron atoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

[Computer-assisted analysis of wall motion of the right ventricle in a normal patient sample and diagnosis of right heart infarction using transesophageal echocardiography].

Using 2D and M-Mode transesophageal short axis cross sections, right ventricular systolic wall motion was quantified in 15 normal patients. A further group of 39 patients with right ventricular infarction was investigated. In the normal group fractional shortening of the septum was -19.6% (-45 to 8%), that of the lateral wall 51.6% (37 to 73%), of the posterior wall 33.9% (5 to 50%) and of the anterior wall 42.7% (18 to 57%). Right ventricular infarction (RVI) was associated in 33 patients with posterior left ventricular infarction (85%) and in three patients with anterior infarction. In two cases only an isolated RVI was found. Right ventricular dilation occurred in 24 patients (61%). Hemodynamic criteria were fulfilled in eleven out of 21 patients (53%). RVI was confirmed in one patient by surgery and in ten patients by autopsy. Recognition of regional wall motion abnormalities by transesophageal echocardiography permits an accurate bedside identification of RVI. 2D and M-Mode registration of the short axis improves RVI assessment. Wall motion analyses offer the possibility to determine the extent of right ventricular infarction.

Adult↗

[Heart involvement in mixed connective tissue disease (MCTD)].

The incidence of cardial involvement in mixed connective tissue disease (MCTD) was investigated by two-dimensional echocardiography. Pericardial manifestation was found in two patients. Mitral valve prolapse was detected in 61% of the patients, which may indicate a specific cardial involvement in MCTD. Myocardial changes were rare.

Adult↗

Results of intracoronary stents for management of coronary dissection after balloon angioplasty.

Dissections after coronary balloon angioplasty are risk factors for acute or subacute vessel closures. Intracoronary stenting was developed to avoid these complications by pressing the intimal and medial flaps against the vessel wall, thus reducing the risk of acute thrombosis. A total of 22 stents were implanted into the coronary arteries of 15 patients with dissections after balloon angioplasty causing angina pectoris or ischemic electrocardiographic changes. Stent delivery was successful in all cases. In 1 patient acute stent thrombosis was documented and treated successfully by thrombolytic therapy. Another patient underwent coronary artery bypass surgery 24 hours later because of persisting angina. Angiograms after 24 hours documented vessel patency in the remaining 14 patients. Late control angiograms after 4 to 6 months were obtained in 12 of 14 patients. Vessel patency without significant restenosis was observed in 8 patients, restenosis in 3 and reocclusion in 1 patient. All 3 patients with multiple stent implantation had restenosis (n = 2) or reocclusion (n = 1), compared with 1 patient with single stent implantation. Thus, intracoronary stenting appears to be a secure and effective method of handling bailout situations caused by dissection after balloon angioplasty, with good long-term results when only a single stent is implanted.

Aged↗

Multicenter registry of angioplasty therapy of cardiogenic shock: initial and long-term survival.

This retrospective multicenter study reviews the role of acute percutaneous transluminal coronary angioplasty in the treatment of cardiogenic shock complicating acute myocardial infarction to determine whether early reperfusion affects in-hospital and long-term survival. From 1982 to 1985, 69 patients were treated with emergency angioplasty to attempt reperfusion of the infarct-related artery. Balloon angioplasty was unsuccessful in 20 patients (group 1) and successful in 49 patients (group 2). Initial clinical and angiographic findings in the groups with unsuccessful and successful angioplasty were similar with respect to age (60.5 +/- 2.3 versus 57 +/- 1.8 years), infarct location (65% versus 65% anterior) and gender (65% versus 67% male). Hemodynamic variables in the two groups, including systolic blood pressure (68 +/- 4.3 versus 73 +/- 1.6 mm Hg), left ventricular end-diastolic pressure (24.4 +/- 2.4 versus 27 +/- 1.0 mm Hg) and initial ejection fraction (28.5 +/- 4% versus 32 +/- 2%), were also similar. Twenty-nine patients received thrombolytic therapy with streptokinase; the overall rate of reperfusion was 34%. Group 1 patients had a short-term survival rate of 20%, compared with 69% in group 2 patients (p less than 0.0005). Thirty-eight patients survived the hospital period and were followed up for 24 to 54 months (mean 32.5 +/- 2.4). Five patients (all in group 2) died during follow-up. The long-term incidence rate of congestive heart failure was 19%, arrhythmia 21%, need for repeat angioplasty 17% and coronary artery bypass grafting 26%. Twenty-four month survival was significantly better in group 2 patients (54%) versus group 1 patients (11%, p = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗

Sudden cardiac death while wearing a Holter monitor.

The Holter tapes of 61 patients (46 men, mean age +/- standard deviation 65 +/- 11 years) with sudden cardiac death while being monitored were analyzed. Thirty-eight patients were known to have coronary artery disease, 5 had cardiomyopathy, and 7 had aortic valve disease. Etiology remained unknown in 11 patients. Mean New York Heart Association functional class was 2.5 +/- 0.7. Thirty patients had received antiarrhythmic drugs and 32 had received digitalis. Sudden death occurred at rest in 73%. In the hours before death, repetitive ventricular arrhythmias were found in 50 patients (82%), with atrial fibrillation in 34%. Patients with bradyarrhythmic death (18%) had less complex ventricular activity compared to patients with tachyarrhythmic death (p less than 0.01). Lethal arrhythmias--monomorphic ventricular tachycardia, polymorphic ventricular tachycardia, torsades de pointes, primary ventricular fibrillation, and 1:1 conducting atrial tachycardia--were found in 26 (43%), 15 (25%), 5 (8%), 3 (5%), and 1 patient, respectively. The coupling interval of the final ventricular tachycardia correlated inversely with the initial frequency of ventricular tachycardia (p less than 0.05). For patients with tachyarrhythmic death, an increase of heart rate within the last 3 hours was noted (83 vs 89 beats/min, p less than 0.05). Ventricular premature complexes and the proportion of patients with greater than 2 couplets and greater than 2 triplets increased significantly only within the last hour before death.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Analysis of high-frequency rotational angioplasty-induced echo contrast.

During high-frequency rotational angioplasty (HFRA), myocardial contrast enhancement (echo contrast) was observed by means of two-dimensional echocardiography. In order to evaluate the echo contrast produced by HFRA, an in vitro experimental model was built using a cylinder with the HFRA catheter scanned in a water bath. The cylinder was filled with blood, mineral water, and distilled water. With a 2.5-MHz transducer, echograms were recorded and analyzed by video intensitometer, and the maximum intensity IUmax and persistence time P were calculated. Rotation frequencies of 20,000-200,000 rpm with 2.0--mm burrs and times of 10 s were tested. In another model, hyperbaric conditions for the same media were produced. The influence of debris from arterioscleroic plaque and of hematocrit on echo contrast intensity were also analyzed. The effect of HFRA on hemolysis (LDH, free hemoglobin) within 10 s and temperature were also measured. The contrast effect was transient, depending on the rotation frequency. In blood, it appeared at 20,000 rpm (IUmax at 200,000 rpm: 237 IU), in mineral water at 40,000 rpm (IUmax 165 IU), and in distilled water at 80,000 rpm (IUmax 72 IU). Persistence time was measured up to about a half-minute. Echo contrast production was reduced at 0.5 bar and fully suppressed at 2.5 bar. Debris increased contrast intensity from about 219 IU to 225 IU (at 160,000 rpm). In blood IUmax decreased from 227 IU to 97 IU by lowering the hematocrit from 44.2% to 3.6%.(ABSTRACT TRUNCATED AT 250 WORDS)

Echocardiography↗

Sublingual administration of captopril in patients with acute myocardial ischemia.

To investigate the anti-ischemic capability of the angiotensin-converting enzyme inhibitor captopril, 10 patients with acute myocardial ischemia (angina pectoris less than 1 h, ST-segment depression greater than or equal to 0.1 mV, no rise in creatine phosphokinase) received 25 mg captopril sublingually after being treated with an intravenous infusion of nitroglycerin (3 mg/h) and heparin (1200 IU/h) for 1 hour. A control group of 10 patients received placebo instead of captopril. Results showed a decrease of the initial ST-segment depression from 0.25 +/- 0.04 to 0.2 +/- 0.03 mV (p less than 0.01) with nitroglycerin for the captopril group and from 0.26 +/- 0.05 to 0.21 +/- 0.05 mV (p less than 0.01) for the control group. An additional decrease to 0.13 +/- 0.03 mV (p less than 0.001) was measured after sublingual captopril, while no significant change was found in the placebo group (0.19 +/- 0.04 mV). In both groups, 3 patients had no incidents of angina after 1-h nitroglycerin infusion. An additional 6 patients resolved their complaints after captopril administration in contrast to only 1 after placebo. Two patients in the placebo group required increased doses of nitroglycerin because of impairment of anginal complaints. Hemodynamic measurements documented a significant drop of pulmonary vascular resistance after a 1-h infusion of nitroglycerin (-12.9% and -13.1%, respectively, p less than 0.05), while all other parameters remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

New developments in the treatment of gastric carcinoma.

The recent successes being achieved with combination chemotherapy regimens strongly indicate that gastric cancer is chemosensitive. With these regimens, objective remission rates of more than 50% were recorded, including approximately 10% complete remission (CRs). The finding that locally advanced disease (LAD) and technically unresectable disease could be rendered resectable by preoperative chemotherapy (EAP) was important. The median survival time was 18 months for all patients and 24 months for disease-free patients. At 30+ months, 21% of all patients are still living disease free. The expected survival of patients with unresectable LAD is approximately 4-6 months without any treatment and 6-9 months with standard chemotherapy. Compared with the latter results, the preoperative use of etoposide, adriamycin, and platinum (EAP) seems to improve the prognosis of patients with LAD. Moreover, such a multimodal approach may increase the number of long-term survivors among patients with resectable gastric cancer, especially those whose stage indicates a high risk of relapse (stage IIIa or IIIb). However, partly because of the severe toxicities (myelo-suppression, nausea/vomiting), a considerable number of patients cannot be treated with these new regimens. Considering the predominantly palliative treatment intentions in far-advanced (metastasized) gastric cancer, regimens with low toxicities and acceptable activity should be preferred. For these reasons, we developed and investigated the combination etoposide, leucovorin, and 5-FU (ELF) in a phase II trial in elderly patients (greater than 65 years) and in patients with cardiac risks who could not be treated with anthracyclines. The overall response rate in 51 evaluable patients was 53%, including six clinical CRs (12%). The median remission duration was 9.5 months and the median survival time was 11 months. Tolerability was excellent. The high remission rate and long medical survival time achieved with ELF, plus its good tolerability, make this combination a valuable alternative to anthracycline-containing regimens. In addition to developing new treatment plans and strategies, it is also desirable to predict treatment outcome with an acceptable degree of certainty. Combinations of variable defined patient subgroups with significantly different probabilities for achieving objective response and for survival. The results of this analysis may contribute to a more patient-oriented and risk-adapted chemotherapy and to better comparability of future studies.

Antineoplastic Combined Chemotherapy Protocols↗

Acute dialysis: PMN-elastase as a new parameter for controlling individual anticoagulation with low molecular weight heparin (Fragmin).

Despite the improvements in the development of dialyzer membranes with greater hemocompatibility, an activation of the coagulation system occurs when blood comes into contact with exogenous surfaces. The large number of heparin dosage regimens demonstrated the difficulty to adapt general therapeutic guidelines. Low molecular weight heparin (Fragmin) was administered as a single bolus dose for anticoagulation during 58 acute dialyses. Anti-Xa-activity, the plasma levels of the lysosomal elastase of the polymorphonuclear granulocytes ("PMN-elastase") and of the thrombin-antithrombin III-complex (TAT) were measured at hourly intervals. Therapeutic anti-Xa-levels did not show evidence of sufficient inhibition of thrombin formation. The PMN-elastase increased by 180 ng/ml 3 h after administration of the bolus dose, with no further increase occurring (plateau phase). This was considered to reflect adequate anticoagulative activity. Where anticoagulation was inadequate, the elastase values rose consistently. After 2 h the increase of the PMN-elastase showed that--and to what extent--coagulation had been activated. The determination of PMN-elastase, using the IMAC-principle, is a method which can be performed quickly with any conventional autoanalyzer. It makes it possible to monitor adequate anticoagulation, but PMN-elastase results must be proven during routine use before recommendation as a routine test.

Acute Kidney Injury↗

High frequency jet ventilation in experimental pulmonary emphysema.

The effects of high frequency jet ventilation (HFJV, f = 2 Hz and 8 Hz, I:E = 0.43, FiO2 = 0.4) were studied and compared with intermittent positive pressure ventilation (IPPV, f = 10-14 breaths/min, VT = 15 ml/kg, I:E = 0.5, FiO2 = 0.4) in 8 dogs before and after induction of panlobular emphysema (PLE). PLE increased alveolar-arterial PO2 difference (PA-aO2) during all modes of ventilation, whereas PaCO2 did not change significantly. In both periods of the study, HFJV8 Hz was less effective in terms of CO2-elimination and oxygenation. In the control-period, functional residual capacity (FRC) was 937 +/- 212 ml. The increase during HFJV (HFJV2 Hz: 1156 +/- 508 ml, HFJV8 Hz: 1153 +/- 433 ml) did not reach significance (P = 0.09). Closing volume (CV) increased from 1.5 +/- 4.3% of vital capacity (%VC) (IPPV) to 6.3 +/- 7.1%VC (HFJV2 Hz) and 10.8 +/- 9.8% VC (HFJV8 Hz), respectively. In the PLE-period, FRC and CV increased significantly to 1107 +/- 207 ml and 14.1 +/- 7.0% VC respectively during IPPV (P less than 0.05). Application of HFJV neither increased FRC (HFJV2 Hz: 1153 +/- 433 ml, HFJV8 Hz: 1005 +/- 344 nor CV 14.8 +/- 6.0% VC and 13.9 +/- 8.1% VC, respectively). It is concluded that HFJV induces no alveolar overdistension in dogs with emphysematous lungs.

Animals↗

Angiotensin II, vasopressin and GTP[gamma-S] inhibit inward-rectifying K+ channels in porcine cerebral capillary endothelial cells.

Cerebral capillaries from porcine brain were isolated, and endothelial cells were grown in primary culture. The whole-cell tight seal patch-clamp method was applied to freshly isolated single endothelial cells, and cells which were held in culture up to one week. With high K+ solution in the patch pipette and in the bath we observed inward-rectifying K+ currents, showing a time-dependent decay in part of the experiments. Ba2+ (1-10 mM) in the bath blocked this current, whereas outside tetraethylammonium (10 mM) decreased the peak current but increased the steady-state current. Addition of 1 microM of angiotensin II or of arginine-vasopressin to the extracellular side caused a time-dependent inhibition of the inward-rectifying K+ current in part of the experiments. Addition of 100 microM GTP[gamma-S] to the patch pipette blocked the K+ inward rectifier. In cell-attached membrane patches two types of single inward-rectifying K+ channels were observed, with single channel conductances of 7 and 35 pS. Cell-attached patches were also obtained at the antiluminal membrane of intact isolated cerebral capillaries. Only one type of K+ channel with g = 30 pS was recorded. In conclusion, inwardly rectifying K+ channels, which can be inhibited by extracellular angiotensin II and arginine-vasopressin, are present in cerebral capillary endothelial cells. The inhibition of this K+ conductance by GTP[gamma-S] indicates that G-proteins are involved in channel regulation. It is suggested that angiotensin II and vasopressin regulate K+ transport across the blood-brain barrier, mediating their effects via G-proteins.

Angiotensin II↗

Platelet-activating factor type activity in plasma from patients with septicemia and other diseases.

The purpose of the present study was to determine whether increased levels of platelet-activating factor (PAF) type activity can be detected in plasma from patients with septicemia and other diseases. A level of PAF below 0.5 ng/mL of plasma was considered normal. We found that plasma from a patient with adverse anaphylactoidic reaction to intravenous analgetics contained 2.1 ng PAF/mL. In seven patients with septicemia, including urosepsis, endocarditis and peritonitis, and with positive blood culture, increased plasma PAF levels (1-20 ng PAF/mL) were observed. Other patients with clinical indications of septicemia had negative blood cultures and/or increased levels of C-reactive protein (CRP). Yet, in the plasma from these patients, no increased PAF levels were detected under the assay conditions used. Two patients with allergic asthma, requiring treatment with steroids, had no measurable plasma PAF. In the plasma from a patient with idiopathic thrombocytopenic purpura (ITP) only an "endogenous" inhibitor of PAF induced platelet aggregation was initially observed. In spite of this, the patient responded to treatment with the PAF antagonist WEB 2086 with a dramatic increase in platelet count (Lohmann et al., Lancet ii, 1147, 1988). Thereafter, also increased PAF levels (3.3 ng PAF/mL) were detected in plasma, although some "endogenous" inhibitor of PAF was still present. In conclusion, increased PAF levels in plasma from patients support a role of PAF in certain human disease states, such as in anaphylactoid reaction, sepsis and septic shock. The type, relevance and specificity of endogenous inhibitors of PAF deserve further study.

Adult↗

PTCA of the left main stem following protective coronary artery bypass grafting.

Percutaneous transluminal coronary angioplasty (PTCA) was performed in 14 patients with significant left main stem stenosis following protective coronary artery bypass grafting (CABG). The procedure was successful in 13/14 patients (93%), achieving a decrease in mean diameter stenosis from 74% +/- 7% to 31% +/- 12% (P less than 0.01). Accordingly, the absolute stenosis diameter increased from 0.9 mm +/- 0.3 mm to 2.4 mm +/- 0.5 mm (P less than 0.01). Dissection of the left main stem artery and a transient significant fall of blood pressure each occurred in one patient. No other serious complications were noted. Eight of 13 patients (62%) with successful PTCA underwent control angiography. Restenosis had occurred in 3 of 8 patients (38%) with total occlusion of the left main stem in 1 patient. All bypass grafts were found to be patent at follow-up. Clinical evaluation in all 14 patients revealed no serious events (death, myocardial infarction, repeat revascularization procedure) during a mean follow-up period of 27 months (range 6-39 months). PTCA of the left main stem following CABG can be considered a relatively safe and effective procedure with a marked restenosis-rate but beyond that, an uncomplicated long-term follow-up.

Adult↗

Identification of abscess formation in native-valve infective endocarditis using transesophageal echocardiography: implications for surgical treatment.

The object of the study was to follow patients with endocarditis-associated abscesses in order to evaluate the clinical outcome with and without surgical intervention. Transesophageal echocardiography successfully displayed the location and extent of abscess cavities in 14 patients (group A) with aortic valve endocarditis. The infective process was limited to the perivalvular tissue in two, extended into the ascending aorta in six, and included the interventricular septum, the right ventricular outflow tract, interatrial septum, and/or mitral valve annulus in six patients. The complication rate was significantly higher in group A than in group B, which consisted of 27 patients with proven signs of endocarditis but without endocarditis-associated abscesses. The complication rates were embolic events 64.3% in group A vs 29.6% in group B, need for surgery in 64.3% vs 18.5%, and death in 50.0% vs 3.7%, respectively. The duration of fever--as a marker of an active infective process--before diagnosis and the onset of adequate treatment was significantly higher in group A than in group B (46.7 +/- 8.4 days vs 7.7 +/- 2.6 days). Organisms were isolated in 71.4% in group A and in all patients of group B. Streptococcal infections were noted in A in 54.5% vs 44.4% in B., staphylococcal in 27.3% vs 40.7%. Initial surgical repair in 9 of 14 patients in A (64.3%) included nine aortic valve and one mitral valve prosthesis implantations, two aortic valve-annulus reconstructive procedures, one dacron patch closure, and three partial resections of the aorta ascendens with end-to-end anastomosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Abscess↗