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Biomedical subjects

C Hamm

Publications and source records attributed to C Hamm.

At least 19 recordsLinked to original sources
PubMed2000

Potassium channel openers and blockers in coronary artery disease. Comparison to betablockers and calcium antagonists.

Potassium channel openers and blockers, which belong to a novel class of vasodilator drugs and to the class of specific bradycardic substances, are potential new antianginal drugs. Experimental findings in vivo suggest that bimakalim is a new substance characterized as ATP-sensitive K+ channel openers, since it exerts preferential vasodilation of the collateral circulation of the coronary vasculature and both leads to increase blood flow to ischemic areas and to attenuate the ST segment elevation caused by regional ischemia in the canine heart. Opening of KATP increases the conductivity of potassium ions which results in hyperpolarization of smooth muscle membranes, thus producing vasodilation. Tedisamil is a new bradycardic agent proven to exert antiischemic and antiarrhythmic effects by blockade of the cellular cardiac repolarization K+ currents as well as of multiple neuronal and vascular K+ currents (Ito, Ik, and K+ATP). Using right heart catheterization and exercise tolerance tests, we investigated the hemodynamic, antiischemic and neurohumoral effects of bimakalim and tedisamil in patients with angiographically proven coronary artery disease, stable angina pectoris and reproducible ST segment depression during exercise. In 50 patients with coronary artery disease, the hemodynamic and antiischemic effects of a single oral dose bimakalim of 0.1 mg, 0.3 mg and 0.6 mg were compared to placebo. In a dose-finding baseline-controlled study, a comparable collective was examined for the effects of acute i.v. administration of tedisamil 0.1, 0.2, 0.3 and 0.4 mg/kg bw. A subgroup of 8 patients receiving 0.3 mg/kg bw tedisamil i.v. was compared with a similar group of 14 patients who had received esmolol (i.v. bolus of 500 micrograms/kg, maintenance dose 200 micrograms/kg/min) and gallopamil (initial dose 0.025 mg/kg, maintenance dose 0.0005 mg/kg/h) in a second intra-individual comparison. Furthermore, in 48 patients, short-term (6 days) effects of tedisamil, 2 times 100 mg orally, were compared to 2 times 50 mg atenolol treatment. With a single oral dose of bimakalim antianginal and/or antiischemic effects were lacking, increased doses, however, induced changes in hemodynamics typical of vasodilation, i.e., a significant decrease in systolic blood pressure and a secondary chronotropic response. In contrast to bimakalim, tedisamil produced antiischemic effects and was found to have favorable hemodynamic, neurohumoral and antiischemic effects in comparison to the betablocker esmolol and atenolol in patients with coronary artery disease. Tedisamil induced a dose-dependent decrease in both heart rate and the index of myocardial oxygen consumption associated with an improvement in ST segment depression. Tedisamil as well as esmolol and atenolol showed almost equipotent antiischemic effects at the doses administered. Compared with gallopamil, both tedisamil and esmolol were superior in their effects on myocardial oxygen consumption and ST segment depression, whereas plasma lactate concentrations were more reduced by tedisamil and gallopamil.

Adrenergic beta-Antagonists↗
PubMed2000

Cardiac sequelae of doxorubicin and paclitaxel as induction chemotherapy prior to high-dose chemotherapy and peripheral blood progenitor cell transplantation in women with high-risk primary or metastatic breast cancer.

Doxorubicin plus paclitaxel has been shown to be an active regimen for metastatic breast cancer and is now frequently used as adjuvant therapy for high-risk primary breast cancer. Initial studies reported a higher than expected rate of cardiac toxicity with this regimen. We studied 105 patients with either high-risk primary breast cancer or metastatic breast cancer who were treated with doxorubicin (60 mg/m2) and 3-h infusions of paclitaxel (175 mg/m2) cycled every 3 weeks. Patients received three cycles of chemotherapy for high-risk primary or four cycles for metastatic disease. Patients then proceeded to high-dose chemotherapy (HDC) (STAMP I cyclophosphamide, cisplatin and carmustine) and peripheral blood progenitor cell transplantation (PBPCT). Patients underwent radionuclide multi-gated angiograms (MUGA) before and following induction chemotherapy and following HDC. During induction chemotherapy 40 (38%) of the patients had a reduction in left ventricular ejection fraction (LVEF). Fourteen had a decrease of 20% or greater and two were mildly symptomatic from CHF. There was additional reduction in the LVEF after HDC with a median value for LVEF of 59% (range, 20-78%). During HDC 10 patients developed clinical signs of congestive heart failure (CHF). Five patients responded to diuretic therapy and did not require any additional treatment. Four patients responded to vasodilation and/or digoxin with improvement in cardiac function. A clinically significant decrease in cardiac function was found in a small number of patients after induction chemotherapy and HDC with PBPCT. The majority of the patients tolerated this regimen without problems. Although there was a decline in LVEF as measured by radionuclide MUGA this did not prevent the majority of patients from proceeding with HDC. Bone Marrow Transplantation (2000).

Adult↗
PubMed2000

Bone marrow and peripheral blood hematopoietic stem cell transplantation: focus on autografting.

This review focuses on certain of the principles involved in high-dose chemotherapy and radiation therapy along with autologous hematopoietic stem cell transplantation for the treatment of certain malignancies. In addition, the evidence, wherever possible based on randomized data, for the application of this approach in certain malignancies is reviewed. The malignancies highlighted include acute myeloid leukemia, acute lymphoblastic leukemia, non-Hodgkin lymphoma, Hodgkin disease, and breast cancer.

Bone Marrow Transplantation↗
PubMed1999

Prehospital testing for troponin T in patients with suspected acute myocardial infarction.

BACKGROUND: Cardiac troponin T (TnT) is a highly sensitive and specific marker for myocardial damage and can be detected early after myocardial injury. Our hypothesis was to use TnT as an objective marker to verify acute myocardial infarction before hospital admission. METHODS AND RESULTS: We evaluated the sensitivity of a rapid qualitative assay for serum TnT for the detection of acute myocardial infarction in the ambulance and assessed the predictive value of a positive prehospital TnT test for death and myocardial infarction during 6-months of follow-up. The study, conducted in an urban area, included 158 consecutive patients with suspected acute myocardial infarction (93 men aged 69 +/- 13 years). A myocardial infarction was confirmed in 40 and excluded in 118 patients. The prehospital TnT test was positive in 11 patients, of whom 7 had acute myocardial infarction. Fifty-three patients had a positive test result at hospital admission, with evidence of myocardial infarction in 39 of them. The sensitivity to acute myocardial infarction was 18% for the prehospital and 98% for the in-hospital test with 78% and 88% specificity, respectively. During follow-up, patients with a positive prehospital TnT test result had cardiac events more often (9 of 11) than patients with a negative result (26 of 147; P <.0001). CONCLUSIONS: In areas with short transport times to the patient the rapid TnT test performed at the point of care identified only a minority of the patients with acute myocardial infarction. A positive prehospital TnT test result seems to be an objective marker for a worse outcome in patients presenting with suspected acute myocardial infarction.

Aged↗
PubMed1999

Cyclophosphamide and paclitaxel as initial or salvage regimen for the mobilization of peripheral blood progenitor cells.

Peripheral blood progenitor cells are now commonly used for hematologic reconstitution after myelosuppressive chemotherapy for hematologic and solid malignancies. The purpose of this study was to evaluate the activity of paclitaxel 170 mg/m2 and cyclophosphamide 2 g/m2 (CP) with filgrastim (human G-CSF) for mobilization of PBPCs as the first or second maneuver after failure with filgrastim alone. Sixty-four patients with stage II-IV breast cancer received (CP) followed by filgrastim (10 microg/kg/day). In 35 (55%) this was the first maneuver while it was for salvage in 29 (45%) patients. The median number of aphereses was two (range, 1-7). In 83% of the patients apheresis was initiated on days 10-11 following chemotherapy. The median numbers of CD34+ cells/kg, CD34+ cells/apheresis/kg and total nucleated cells/kg collected were 8.7 x 10(6) (2.11-73.5), 3.97 x 10(6) (0.3-36.75) and 164.15 x 10(8) (9-660), respectively. All the patients yielded at least 2 x 10(6) CD34+ cells/kg. CP mobilization salvaged the 29 patients who failed mobilization with filgrastim alone. When used as first-line mobilization the yield of CD34+ cells x 10(6)/kg was higher than in the salvage group (16.93 vs 3.94, P < 0.001). Patients receiving CP as salvage reached the target of 5 x 10(6) CD34+ cells/kg in only 45% (13/29) of cases vs 94.3% as first maneuver. CP followed by filgrastim is a safe and effective regimen for the mobilization of PBPCs in patients with breast cancer and shows significant activity in patients who failed to mobilize with filgrastim, suggesting a higher mobilization potential.

Adult↗
PubMed1998

Intravascular ultrasound-guided optimized stent deployment. Immediate and 6 months clinical and angiographic results from the Multicenter Ultrasound Stenting in Coronaries Study (MUSIC Study)

OBJECTIVES: A study was set up to validate the safety and feasibility of intravascular ultrasound-guided stenting without subsequent anticoagulation, and its impact on the 6 months restenosis rate. METHODS: The study was designed to be multicentred, prospective, and observational. RESULTS: One hundred and sixty-one patients with stable angina and a de novo coronary artery lesion were enrolled. In four patients, the implantation of a Palmaz-Schatz (with spiral bridge) stent had failed. One of these four patients died 3 days following bypass surgery. In two other patients, intravascular ultrasound assessment was not performed. One hundred and twenty-five of the remaining 155 patients (81%) were treated with aspirin (100 mg x day(-1)), because all three criteria for optimized stent expansion were met. Twenty-two of the remaining 38 patients (25%), in whom at least one criterion was not met were treated with aspirin and acenocoumarol (3 months, INR 2.5-3.5), while 16 patients only received aspirin. Stent thrombosis was documented in two patients (1.3%) for which repeat angioplasty was performed. During the hospital stay, there were no deaths or Q-wave myocardial infarctions. Five patients (3.2%) sustained a non-Q-wave myocardial infarction. During the follow-up period (198+/-38 days, complete for all patients, except one), one patient (0.6%) sustained a Q-wave myocardial infarction, one (0.6%) underwent bypass surgery, and repeat angioplasty was performed in nine patients (5.7%). In two of the nine patients, repeat angioplasty involved another lesion. Therefore, the target lesion revascularization rate during follow-up was 4.5% (seven patients). At quantitative coronary angiography, the minimal lumen diameter (mean+/-SD) increased from 1.12+/-0.34 mm before to 2.89+/-0.35 mm after stenting. Repeat angiography at 6 months was performed in 144 patients (92%). The minimal lumen diameter at follow-up was 2.12+/-0.67 mm. Restenosis (diameter stenosis of 50% or more) was documented in 12 patients or 8.3%. When the two patients with documented stent thrombosis are included, the restenosis rate amounts to 97%. CONCLUSIONS: These data confirm that, in selected patients, stents can safely be implanted without the use of systemic anticoagulation, provided optimal stent expansion is achieved. The exact role of intravascular ultrasound in the achievement of these results needs to be established by appropriately designed studies. In the meantime, intravascular ultrasound coupled with the Palmaz-Schatz stent incorporating a spiral bridge, may have contributed considerably to the immediate angiographic outcome, which in turn may explain the favourable clinical and angiographic outcome at 6 months.

Aged↗
PubMed1998

Percutaneous closure of secundum atrial septal defect with a new self centering device ("angel wings").

OBJECTIVE: To investigate the safety, efficacy, and clinical application of a new self centering device ("angel wings") for closure of secundum atrial septal defects (ASD II) and persistent foramen ovale in all age groups. DESIGN: Multicentre, prospective, nonrandomised study. PATIENTS INCLUSION CRITERIA: defects with an occlusive diameter of < or = 20 mm and a surrounding rim of > 4 mm; body weight > 10 kg; and an indication for surgical closure of secundum atrial septal defect. Additionally, there were compassionate indications for closure in patients with persistent foramen ovale. INTERVENTIONS: Defects were closed by a transcatheter device consisting of two square frames made of superelastic nitinol wire. The frames are covered by elastic polyester fabric, which is sewn together at a central circle. All procedures, except for three interventions that were carried out under sedation, were performed under general anaesthesia using transoesophageal echocardiography and fluoroscopy to monitor intervention. RESULTS: Closure was attempted in 75 (71%) of 105 patients. An ASD II was present in 35 children and 15 adults. A persistent foramen ovale was present in 25 adults with suspected paradoxical embolism. Transcatheter closure was unsuccessful in three children and crossover to surgery was required. Residual shunts were found in 20 patients (27%) immediately after the procedure. A transient atrioventricular third degree block occurred in three patients (4%) and the right atrial disk was not fully deployed in three. A minor shunt (< 3 mm) was present in only three (4%) of 72 patients during follow up of 1-17 months. Blood clots on the right atrial disks in two patients (one required lysis) were seen during follow up transoesophageal echocardiography. Serious complications demanding surgical removal of the device occurred in three patients. One patient had haemopericardial tamponade because of an aortic lesion. Left atrial thrombus formation due to an unfolded right atrial disk was found in a second patient and dislodgement of the left atrial disk resulted in a large residual shunt in a third. CONCLUSIONS: Percutaneous closure of a central ASD with a diameter < or = 20 mm in paediatric and adult patients is feasible and effective with this new device. It is a promising alternative to surgical closure. Modifications of the design, however, seem to be mandatory as 4% of patients developed serious complications.

Adolescent↗
PubMed1997

Recanalization of total coronary occlusions using a laser guidewire (the European TOTAL Surveillance Study).

The success rates of coronary angioplasty for the treatment of chronic total occlusions are less favorable than for coronary stenosis. Therefore, a new laser guidewire (LW) was designed to facilitate the crossing of chronic total occlusions. We report on the results of a European multicenter surveillance study, evaluating the laser guidewire performance. Between May 1994 and July 1996, 345 patients (age 59 +/- 10 years, 291 men) with chronic total occlusions were enrolled in 28 European centers. The median age of occlusion was 29 weeks (range 2 to 884), the occlusion length 19 +/- 10 mm. LW recanalization was successful in 205 patients (59%/). LW perforation occurred in 73 patients (21%), with hemodynamic consequences in 4 (1%). There were no deaths, emergency coronary artery bypass graft surgery, or Q-wave myocardial infarctions. In a multivariate regression analysis an occlusion age of <40 weeks (p = 0.001, RR = 1.34) and an occlusion length <30 mm (p = 0.01, RR = 1.59) were independent predictors of success. Results indicate that the LW is an effective and safe tool in the treatment of chronic total occlusion refractory to conventional guidewires.

Chronic Disease↗
PubMed1997

Comparison of saruplase and alteplase in acute myocardial infarction. SESAM Study Group. The Study in Europe with Saruplase and Alteplase in Myocardial Infarction.

Four hundred seventy-three patients with acute myocardial infarction (AMI) were treated with either saruplase (80 mg/hour, n = 236) or alteplase (100 mg every 3 hours, n = 237). Comedication included heparin and acetylsalicylic acid. Angiography was performed at 45 and 60 minutes after the start of thrombolytic therapy. When flow was insufficient, angiography was repeated at 90 minutes. Coronary angioplasty was then performed if Thrombolysis In Myocardial Infarction (TIMI) trial 0 to 1 flow was seen. Control angiography was at 24 to 40 hours. Baseline characteristics were similar. Angiography showed comparable and remarkably high early patency rates (TIMI 2 or 3 flow) in both treatment groups: at 45 minutes, 74.6% versus 68.9% (p = 0.22); and at 60 minutes 79.9% versus 75.3% (p = 0.26). Patency rates at 90 minutes before additional interventions were also comparable (79.9% and 81.4%). Angiographic reocclusion rates were not significantly different: 1.2% versus 2.4% (p = 0.68). After rescue angioplasty, angiographic reocclusion rates of 22.0% and 15.0% were observed. Safety data were similar for both groups. Thus, (1) early patency rates were high for saruplase and alteplase treatment, (2) reocclusion rates for both drugs were remarkably low, and (3) complication rates were similar. Thus, saruplase seems to be as safe and effective as alteplase.

Aged↗
PubMed1997

Pharmacodynamic modelling of the analgesic effects of piritramide in postoperative patients.

BACKGROUND: The concentration-effect relationship of piritramide, a synthetic opioid analgesic predominantly used for postoperative analgesia and analgosedation, has not been reported so far. METHODS: Twenty-four patients of both genders aged 58.1 (11.7) yr (mean (SD)) received inhalational anaesthesia for abdominal surgery. Postoperative pain was assessed with a visual analogue scale (VAS). Analgesia was provided with piritramide, infused at a rate of 7 micrograms.kg-1.min-1 until analgesia was considered sufficient (VAS < 25) or up to a maximum dose of 0.2 mg/kg. The plasma concentrations of piritramide were determined by gas chromatography. An inhibitory fractional sigmoid Emax-model was used to describe the relation between effect site concentration and perceived pain. RESULTS: The equilibration half-life between plasma and effect site concentrations (T1/2 (keo)) was 16.8 min (median; range: 4.4-41.6 min). The steady-state plasma concentration required to produce 50% of maximum analgesia (EC50) was 12.1 ng/ml (range: 2.9-29.8 ng/ml) and correlated with initial pain intensity. The slope factor gamma was 1.9 (range: 0.5-6.1) and increased with age. Clinically relevant respiratory depression did not occur. Due to the relatively large equilibration half-life of the effect compartment, the context-sensitive half-time of the effect site concentrations after short-time administration (< 2 h) clearly exceeded those of alfentanil, sufentanil, and fentanyl. CONCLUSIONS: The analgesic effect of piritramide was adequately described by an inhibitory fractional Emax-model. In order to overcome the pronounced hysteresis, piritramide should initially be administered as an intravenous bolus of at least 5 mg.

Adult↗
PubMed1996

Angiographic follow-up results of a randomized study on angioplasty versus bypass surgery (GABI trial). GABI Study Group.

Although several randomized trials have been performed to compare the outcomes of percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass surgery (CABG) in patients with multivessel disease, there is little data available on angiographic follow-up results. The present substudy of the German angioplasty versus bypass surgery investigation (GABI Trial) compares the angiographic revascularization status in these two cases 6 months after treatment. Follow-up angiograms were available in 102 CABG patients and 117 PTCA patients. Although the protocol excluded patients with total occlusion, on follow-up 6 months after treatment we found total occlusion of 94 native arteries (36.9%) in the CABG group and of six arteries (2.5%) in the PTCA group (P < 0.001). The rate of occluded native vessels did not correlate significantly with the severity of the lesion before bypass surgery. In the CABG group 31 bypass grafts (12.2%) were found to be occluded at the 6 month follow-up examination (29/225 vein grafts [12.9%]; 2/30 mammary artery grafts [6.7%]). The main pathway, defined as the nutrient vessel (native vessel or bypass graft) providing the least resistance to blood flow, was narrowed by a lesion with a diameter stenosis of 70-100% for 36 target lesions (14.1%) in the CABG group and 39 target lesions (16.2%) in the PTCA group (P, ns). However, the prevalence of moderately severe lesions with a 50-69% diameter reduction of the main pathway was significantly greater in the PTCA group (44 lesions, 18.3%) than in the CABG group (19 lesions, 7.5%, P < 0.01). Thus, 6 months after randomized allocation to PTCA or CABG, we found comparable rates of high-grade lesions in the main pathways of both treatment groups. Whereas moderately severe lesions of the main pathway were predominantly seen in the PTCA group, there was marked disease progression to total occlusion in the native circulation after bypass grafting.

Aged↗
PubMed1996

[Initial clinical and angiographic results with the AVE Micro-Stent].

UNLABELLED: The AVE Micro Stent is a flexible stent with a small surface. Aim of this study was to investigate safety and efficacy of this stent. 105 AVE Micro Stents were deployed in 78 lesions in 64 patients. The implantation was performed electively (19%), after unsatisfactory PTCA (59%), and as "bailout" (23%) into left main (1), LAD (23), LCX (15), RCA (19) or CABG (6). Minimal lumen diameter and percent diameter stenosis were measured by quantitative coronary angiography before and after interventions and, in 21 patients, after 3 months. Stent-implantation was successful in 62 of 64 patients. The passage of the AVE Micro Stents through deployed stents (46) was successful in all of 28 cases. There were no deaths or myocardial infarctions. In two patients, subacute thromboses with subsequent increase of CK occurred, which were successfully treated. The minimal lumen diameter was 0.77 +/- 0.62 mm before intervention, 2.98 +/- 0.48 mm after implantation (p < 0.001), and 2.03 +/- 1.21 after 3 months (p < 0.001). The percent diameter stenosis was 75 +/- 20% before intervention, 39 +/- 20% after PTCA and 0 +/- 12% after implantation (p < 0.001). After 3 months, six of 21 patients (29%) with follow-up angiography had a restenosis, defined as > 50% diameter stenosis compared with the reference vessel. CONCLUSIONS: 1) The AVE Micro Stent is a flexible stent, which can be safely and efficiently deployed even through implanted stents. 2) The AVE Micro Stent appears to be particularly suitable for "bailout" therapy of dissections. 3) The rate of subacute thrombosis was low with this stent.

Adult↗
PubMed1994

Efficacy of high dose intravenous heparin for treatment of left ventricular thrombi with high embolic risk.

OBJECTIVES: This study was performed to assess the efficacy of high dose intravenous heparin to treat mobile or protruding left ventricular thrombi as detected by serial echocardiography. BACKGROUND: The presence of mobile and protruding left ventricular thrombi greatly increases the risk of arterial embolization, yet optimal therapy, be it thrombolysis, anticoagulation or surgical removal, has not been defined. METHODS: Full dose heparin, 31,291 +/- 7,980 (mean +/- SD) IU/day, to prolong partial thromboplastin time to at least twice normal, was administered intravenously to 23 consecutive patients with 25 mobile and protruding thrombi. Patients were prospectively evaluated for hemorrhagic complications and embolic events during therapy. The presence or absence of thrombi and their size and characteristics were assessed by serial echocardiography. RESULTS: In all 23 patients left ventricular thrombi decreased in size, with disappearance of the high risk features. The duration of high dose heparin infusion was 7 to 22 days (mean 14 +/- 4). Thrombus size was reduced from 3.9 +/- 2.6 to 0.16 +/- 0.38 cm2, and thrombus disappeared entirely in 19 (83%) of 23 patients. No embolic events were detected during treatment, and the only complication was an upper gastrointestinal hemorrhage that was successfully treated medically. CONCLUSION: High dose intravenous heparin is a highly effective and safe treatment for completely resolving left ventricular thrombi with high risk features for embolization. Most such thrombi disappear completely within 1 to 3 weeks of this treatment without embolic or hemorrhagic complications.

Echocardiography↗