The effect of fenofibrate (a clofibrate derivative) on fibrinogen concentration, blood viscosity and myocardial microcirculation was examined in 35 patients with coronary heart disease (n = 27) or hypertension (n = 8). After eight weeks' administration of 250 mg fenofibrate daily cholesterol and triglycerides levels decreased significantly, as did the fibrinogen concentration, from a mean of 300.7 +/- 75.1 mg/dl to 252.3 +/- 61.2 mg/dl (P less than 0.01). Plasma viscosity and erythrocyte aggregation were also significantly lowered (from 1.43 +/- 0.09 to 1.37 +/- 0.07 mPas and 15.0 +/- 3.1 to 13.5 +/- 2.2, respectively; P less than 0.01). In eight of twelve subjects selected from the whole group thallium myocardial scintigraphy demonstrated, after eight weeks of treatment with fenofibrate, a global (in two) or regional (in six) increase in blood flow. Reduction of fibrinogen concentration may in coronary heart disease achieve an improvement in myocardial microcirculation with decreased myocardial ischaemia.

To assess the effect of urokinase-induced reduction of fibrinogen concentration on myocardial perfusion, urokinase infusions were administered for 3 months to 24 men (mean age 59 +/- 10 years) in the inoperable end-stage of coronary heart disease with treatment-resistant angina pectoris. Initially 500,000 IU urokinase were infused i.v. daily until a fibrinogen concentration of 150-200 mg/dl was reached. Treatment was then continued as out-patients at a dosage of 500,000 IU two to four times per week. After 12 weeks the fibrinogen concentration had fallen from 348 +/- 88 to 211 +/- 52 mg/dl and plasma viscosity from 1.44 +/- 0.08 to 1.33 +/- 0.09 mPa.s (P for each less than 0.01). Up to the end of 12 weeks after the end of treatment the frequency of anginal attacks fell significantly from 3.2 +/- 1.6 to 0.7 +/- 0.4 daily (P less than 0.01), while ergometric exercise capacity increased by 76%. Thallium myocardial scintigraphy demonstrated an increased perfusion in all but three of 19 patients, global in 10, regional in 6. These results indicate that in patients with treatment-resistant angina due to coronary heart disease chronic intermittent urokinase infusion provides a promising treatment alternative.

DNA distribution patterns and the fractions of the cell cycle phases were determined by means of flow-through cytometry in 87 samples of normal, atrophic, hyperplastic and carcinomatous human endometrium. The S-phase fractions vary during the normal menstrual cycle between 1 and 3% and reach a periovulatory maximum between 4.4 and 4.7%. Atrophic endometrium and regressive glandular cystic hyperplasia have little DNA synthesis (1.01% and 1.68% S-phase fractions respectively). Proliferating glandular cystic hyperplasia reveals 3.38% S-phase fraction, whereas adenomatous hyperplasia has an increased number of DNA-synthesizing cells (4.81%). The well-differentiated endometrial carcinoma shows no cytophotometrically detectable differences in comparison to adenomatous hyperplasia. All endometrial samples except for poorly differentiated endometrial carcinoma showed a diploid to tetraploid DNA distribution pattern. The poorly differentiated endometrial carcinoma displays two different types: one rapidly growing diploid-tetraploid tumor with 8.0 to 9.6% S-phase fractions, and another type with stemline deviations, polyploid nuclei and less pronounced synthetic activity.

Purpose: The aim of the current study was to determine the overall diagnostic accuracy of Tc-99m-labeled antigranulocyte monoclonal antibody Fab' fragments (LeukoScan) for the routine detection of bone and soft tissue infections in a retrospective evaluation.Patients and Methods: 138 patients (63 men, 75 women; mean age, 58.29 +/- 25.38 years) with fever of unknown origin and possible endocarditis (n = 59), infection of arthroplastic joints (n = 20), arthritis (n = 16), peripheral (n = 15) and central bone infections (n = 14), soft tissue infection (n = 6), appendicitis (n = 4), pericarditis (n = 2), or vascular graft infection (n = 2) underwent imaging after injection of 555 to 925 MBq (15 to 25 mCi) Tc-99m-labeled antigranulocyte monoclonal antibody Fab' fragments (LeukoScan).Results: True-positive results were found in 63 of 81 lesions. The overall sensitivity and specificity were 76% and 84%, respectively. In arthritis, seven of seven foci could be detected, whereas false-negative results were found in infections of the femoral bone in three of nine lesions and in periprosthetic infections of long bones in three of eight lesions. Good results were found in five of six soft-tissue infections, in four of six patients with endocarditis, in three of four atypical cases of appendicitis, in two of two infected vascular grafts, and in one of one patient with pericarditis. Subacute and chronic infections of the spine always showed photopenic areas in eight of eight patients. If photopenic lesions were included as diagnostic criteria, the sensitivity and specificity were 88% and 67%, respectively.Conclusions: Tc-99m-labeled antigranulocyte monoclonal antibody Fab' fragments can be used for imaging acute infections of peripheral bones and soft tissues. False-negative results are likely in patients with chronic infections. Sensitivity can be increased while decreasing specificity by including photopenic lesions in the spine as diagnostic criteria for localizing disease.

Purpose The aim of the current study was to determine the overall diagnostic accuracy of Tc-99m–labeled antigranulocyte monoclonal antibody Fab’ fragments (LeukoScan) for the routine detection of bone and soft tissue infections in a retrospective evaluation. Patients and Methods 138 patients (63 men, 75 women; mean age, 58.29 ± 25.38 years) with fever of unknown origin and possible endocarditis (n = 59), infection of arthroplastic joints (n = 20), arthritis (n = 16), peripheral (n = 15) and central bone infections (n = 14), soft tissue infection (n = 6), appendicitis (n = 4), pericarditis (n = 2), or vascular graft infection (n = 2) underwent imaging after injection of 555 to 925 MBq (15 to 25 mCi) Tc-99m–labeled antigranulocyte monoclonal antibody Fab’ fragments (LeukoScan). Results True-positive results were found in 63 of 81 lesions. The overall sensitivity and specificity were 76% and 84%, respectively. In arthritis, seven of seven foci could be detected, whereas false-negative results were found in infections of the femoral bone in three of nine lesions and in periprosthetic infections of long bones in three of eight lesions. Good results were found in five of six soft-tissue infections, in four of six patients with endocarditis, in three of four atypical cases of appendicitis, in two of two infected vascular grafts, and in one of one patient with pericarditis. Subacute and chronic infections of the spine always showed photopenic areas in eight of eight patients. If photopenic lesions were included as diagnostic criteria, the sensitivity and specificity were 88% and 67%, respectively. Conclusions Tc-99m–labeled antigranulocyte monoclonal antibody Fab’ fragments can be used for imaging acute infections of peripheral bones and soft tissues. False-negative results are likely in patients with chronic infections. Sensitivity can be increased while decreasing specificity by including photopenic lesions in the spine as diagnostic criteria for localizing disease.

Persisting perfusion defects may still be found in pulmonary perfusion scintigraphy months or years after pulmonary embolism. The aim of this study was to investigate the rate of persisting perfusion defects and the pattern of scintigraphic follow-up of patients after pulmonary embolism. Only those patients were included into our study who received pulmonary perfusion scintigraphy between 1991 and 1999, and who had perfusion defects including at least one whole segment. These perfusion defects were considered as persisting perfusion defects if unchanged over at least 1 year. From 3640 patients examined, 451 (12.4%) had perfusion defects meeting the criteria of this study. Of those, 129 (28.6%) received a scintigraphic follow-up. In 62 patients (48.1%), a reperfusion of the defects was found. In 38 patients (29.5%), the defects persisted within a follow-up period of up to 12 weeks. However, no pulmonary perfusion scintigraphy was performed thereafter. Out of the 129 patients receiving a scintigraphic follow-up, only 29 (22.5%) had a follow-up over more than 1 year, 19 of those had persisting perfusion defects. It is concluded that our data show an inadequate scintigraphic follow-up of patients with pulmonary embolism which may lead to unnecessary anticoagulant treatment if persisting perfusion defects are misinterpreted as fresh pulmonary embolism. In many cases, there was no further follow-up even if reperfusion of the defects was lacking in early follow-up.

A 49-year-old man had a histologically confirmed pancreatic carcinoma with several huge necrotic metastases in the liver. Many cases of increased radionuclide uptake in liver metastases have been reported, but in this case the radionuclide uptake was missing.

Despite the advances made in direct myocardial revascularisation by surgical as well as interventional techniques, there is an increasing number of highly symptomatic patients for whom for none of these methods are suited. This has led to a renewed interest in techniques of indirect myocardial revascularisation, which were abandoned years ago because of the success achieved with bypass grafting and PTCA. Transmyocardial laser revascularisation has picked up the idea of transmural channels, filling with blood from the left ventricle, as first described by Sen et al. in 1965 [4]. Primarily used in combination with coronary bypass grafting, it has now become a sole therapy for end-stage coronary artery disease. While the mechanism of action of this new indirect procedure is still not quite clear, clinical improvements have been demonstrated in numerous studies.

Zum Thema Die inflammatorische Kardiomyopathie entspricht einer akuten oder chronischen Myokarditis mit kardialer Dysfunktion. Bei der chronischen Myokarditis, bei den idiopathischen Kardiomyopathien und den Vaskulitiden, z.B. im Rahmen von Systemerkrankungen (Sakroidose, Kollagenose), wurden wiederholt ischämische Syndrome mit Angina pectoris, pathologischem Belastungs-EKG und ischämietypischen Veränderungen, auffälligen Thallium- und Testa-MIBI Szintigrammen beschrieben, obgleich die epikardialen Koronargefäße weit und ohne stenotische Einengungen waren. Small Vessel Disease, Syndrom X, Vaskulitis bei Myokarditis, Spasmustheorie oder Tonusdysregulation waren hypothetische Denkmodelle für die atypische Angina pectoris oder die falsch positiven Myokardszintigramme. Für diese Beobachtungen stellen heute am ehesten die durch Zytokine veränderte Regulationsbreite der kardialen mikrovaskulären Strombahn neben einer echten Vaskulitis oder einer sekundären Immunpathogenese den größten gemeinsamen Nenner dar.

Transmyocardial laser revascularization (TMLR) is a new technique for patients with CAD or heart attack to revascularise ischemic areas of the myocardium in which the localisation or the condition of the vessels does not allow bypass grafting.

There is a subgroup of patients with coronary artery disease who are refractory to the therapeutical methods so far applied. We report on 128 patients who fulfill this definition and have therefore undergone pure transmyocardial laser revascularisation (TMLR) or transmyocardial laser revascularisation in combination with coronary bypass surgery at our institution. The patients can be characterized by a long history of coronary artery disease with multiple revascularizing procedures, e. g. bypass surgery or percutaneous transluminal coronary angioplasty (PTCA), pronounced symptoms of coronary artery disease and chronic heart failure in the presence of markedly reduced left ventricular ejection fractions and intense antiischemic medical therapy. The patients were 62.2±9.8 (SD) years of age, in 89.9% of them at least one bypass operation and in 44.5% up to more than three percutaneous transluminal coronary angioplasties (PTCAs) had been performed prior to TMLR. There was a history of myocardial infarction in 90.7% of patients and 89.8% were in the Canadian Cardiovascular Society (CCS) classes III or IV and 94.5% of them were in the NYHA classes III or IV. The left ventricular ejection fraction was 49.5±16.4% and all of the patients were under intense antiischemic medical treatment which included nitrates or molsidomine in 96.9%, beta blockers in 53.1%, angiotensin converting enzyme inhibitors (ACE inhibitors) in 44.5%, digitalis in 22.7% and diuretics in 52.3% of patients. The preoperative data on myocardial viability, inducible ischemia and coronary morphology provided important clinical information for the decision, which revascularizing method would be the most appropriate for each vessel or myocardial region. This had to be weighed against the patient’s operative risk, which is predominantly determined by the left ventricular ejection fraction, the arteriosclerotic involvement of the remaining vascular system and concomitant diseases, particularly of pulmonary origin.

Das Endstadium der koronaren Herzkrankheit ist gekennzeichnet durch schwerste und diffuse Veränderungen der Herzkranzgefäße, die schließlich den direkten Revaskularisationsverfahren wie PTCA oder Bypass-Chirurgie nicht mehr zugänglich sind. Auch unter maximaler antianginöser Therapie bleibt häufig eine schwere Angina-pectoris-Symptomatik bestehen, so daß zur Behandlung dieser Patienten doch indirekte Revaskularisationsverfahren wieder an Bedeutung gewonnen haben. Bei der transmyokardialen Laserrevaskularisation (TMLR) soll mit Hilfe transmuraler Kanäle und einem Anschluß an intramyokardiale Gefäße eine Blutversorgung des Myokards aus dem Ventrikel gewährleistet werden. Unterschiedliche Modelle sind dabei zur Funktion der Kanäle entwickelt worden. So wurde zunächst von einer „Reptilisation des Herzens” gesprochen, vorstellbar sind auch Analogien zu natürlicherweise existierenden ventrikulokoronaren Verbindungen, und schließlich wird auch eine Induktion der Neoangiogenese durch das Lasertrauma diskutiert. Während hier noch eine endgültige Klärung durch experimentelle Daten und Untersuchungsbefunde aussteht, haben mehrere klinische Studien sowohl in USA als auch in der Bundesrepublik Deutschland eine signifikante Verbesserung der Symptomatik und des Behandlungsbedarfs bei über zwei Drittel der mit dieser Methode therapierten Patienten nachweisen können.

Endstage coronary artery disease still remains a therapeutic challenge. An increasing number of patients is no longer amenable for direct revascularization by PTCA or coronary bypass surgery and does also no longer respond to maximum medical therapy. This fact has directed the interest again towards surgical techniques of indirect revascularization, which had been introduced by Beck and other surgeons more than 60 years ago. Among these attempts we can also find transmyocardial needle punctures, firstly performed by Sen in Bombay. In the early eighties it was Mirhoseini, who used a laser for creating these transmural channels, primarily in combination with coronary bypass surgery at the arrested heart and later on together with Crew as a sole therapy at the beating heart. The idea behind this transmyocardial laser revascularization (TMLR) was a "reptilization" of the human heart, which meant a direct blood supply from the ventricle into the ischemic myocardium. Whereas this theory has not proven to be true, as the surface area of these channels is not sufficient for the nutrition of the surrounding myocardial tissue by diffusion or convection, different models have been developed by anatomical, experimental and clinical studies, such as the connection between the laser channels and intramyocardial vessels or capillaries, analogous to ventriculo-coronary connections in human anatomy or pathology as for example those connections described in children with pulmonary atresia and intact ventricular septum or the Thebesian veins. Moreover the laser trauma may also simply contribute to the induction of neoangiogenesis. While the function of TMLR is still not clearly defined, clinical studies in the United States and also in other countries have proven the clinical efficacy in a cohort of severely diseased patients undergoing this procedure. Accordingly more than 2/3 of all patients after TMLR showed a significant improvement of more than 2 angina classes (CCS) as well as a decrease in medication and hospitalization. Moreover there was also a reduction of ischemic areas demonstrated by szintigraphy and, in one study from Houston, also by positron emission tomography. While the overall mortality in all those studies is still considerably high, a reduction could be achieved by a stricter selection of patients excluding especially those with a severely impaired left ventricular function. As demonstrated by preliminary data from the last phase III FDA-study, TMLR may even reduce long-term mortality compared to maximum medical therapy in a randomized group of patients. Our own experiences in 134 patients also confirmed a significant reduction of angina after TMLR alone (n = 67) or in combination with bypass surgery (n = 67) with the majority of patients being in angina class 1 and 2 (CCS) 6 months after surgery. All of these patients were in angina class 3 and 4 before surgery. Nuclear scans could demonstrate an improved perfusion in more than 40%. Further studies as well as other clinical and also experimental investigations have still to be awaited, before the definitive role of TMLR within the armamentarium against coronary artery disease can be determined. However, it is already a therapeutic option for those highly symptomatic patients, who cannot be offered a different treatment modality.

Endstage coronary artery disease still remains a therapeutic challenge. An increasing number of patients is no longer amenable for direct revascularization by PTCA or coronary bypass surgery and does also no longer respond to maximum medical therapy. This fact has directed the interest again towards surgical techniques of indirect revascularization, had been introduced by Beck and other surgeons more than 60 years ago. Among these attempts we can also find transmyocardial needle punctures, firstly performed by Sen in Bombay. In the early eighties it was Mirhoseini, who used a laser for creating these transmural channels, primarily in combination with coronary bypass surgery at the arrested heart and later on together with Crew as a sole therapy at the beating heart. The idea behind this transmyocardial laser revascularization (TMLR) was a "reptilization" of the human heart, which meant a direct blood supply from the ventricle into the ischemic myocardium. Whereas this theory has not proven to be true, as the surface area of these channels is not sufficient for the nutrition of the surrounding myocardial tissue by diffusion or convection, different models have been developed by anatomical, experimental and clinical studies, such as the connection between the laser channels and intramyocardial vessels or capillaries, analogous to ventriculo-coronary connections in human anatomy or pathology as for example those connections described in children with pulmonary atresia and intact ventricular septum or the Thebesian veins. Moreover the laser trauma may also simply contribute to the induction of neoangiogenesis. While the function of TMLR is still not clearly defined, clinical studies in the United States and also in other countries have proven the clinical efficacy in a cohort of severely diseased patients undergoing this procedure. Accordingly more than 2/3 of all patients after TMLR showed a significant improvement of more than 2 angina classes (CCS) as well as a decrease in medication and hospitalization. Moreover there was also a reduction of ischemic areas demonstrated by szintigraphy and, in one study from Houston, also by positron emission tomography. While the overall mortality in all those studies is still considerably high, a reduction could be achieved by a stricter selection of patients excluding especially those with a severely impaired left ventricular function. As demonstrated by preliminary data from the last phase III FDA-study, TMLR may even reduce long-term mortality compared to maximum medical therapy in a randomized group of patients. Our own experiences in 134 patients also confirmed a significant reduction of angina after TMLR alone (n = 67) or in combination with bypass surgery (n = 67) with the majority of patients being in angina class 1 and 2 (CCS) 6 months after surgery. All of these patients were in angina class 3 and 4 before surgery. Nuclear scans could demonstrate an improved perfusion in more than 40%. Further studies as well as other clinical and also experimental investigations have still to be awaited, before the definitive role of TMLR within the armamentarium against coronary artery disease can be determined. However, it is already a therapeutic option for those highly symptomatic patients, who cannot be offered a different treatment modality.

Indications for interventional catheter techniques and bypass surgery have been extended to more complex lesions and also the number of reoperations after primary successful interventions has increased due to progression of the underlying disease. Finally a number of patients remains still symptomatic but, as a consequence of a very diffuse distribution of atherosclerotic lesions, is no longer accessible with conventional techniques of direct revascularization. This has drawn the attention again to indirect techniques of myocardial revascularization. Transmyocardial laserrevascularization offers a new option in reperfusing the ischemic myocardium via transmural channels from the ventricular cavity. As to the function of the channels, it is not quiet clear, wether they may connect to intramyocardial capillaries or may themselves induce a neoangiogenesis. However the clinical follow up in patients with intractable angina pectoris shows a significant improvement. At our hospital a number of 117 patients have been treated with this new method, 53 of them in conjunction with conventional bypass surgery. Clinical follow up after three and six months postoperatively showed a significant improvement concerning angina (CCS) and exercise tolerance (NYHA). This could also objectively be demonstrated by scintigraphy with an increased myocardial perfusion in 50% of the reinvestigated patients. Ischemic areas can still be seen, but occur at a significantly higher exercise level, demonstrating an improved but not normalized myocardial blood supply. The transmyocardial laserrevascularization is no alternative to well established procedures like PTCA or bypass surgery, but can be seen as a therapeutic option for those symptomatic patients recently being intractable. Further longterm studies and also experimental investigations have to evaluate the definitive role of this new treatment for endstage coronary heart disease.

Double-phase single radionuclide parathyroid scintigraphy with Tc-99m-Sestamibi was performed in 26 patients with primary and in 9 patients with secondary hyperparathyroidism. The Tc-99m-Sestamibi-scan identified and localized 21 of 26 adenomas in the 26 patients with pHPT. In only 6 of the 9 patients with parathyroid hyperplasia a focally increased uptake was found. The cause of one false positive result in 5 control patients was an increased Tc-99m-Sestamibi-uptake in a follicular adenoma of the thyroid gland. Parathyroid scintigraphy using Tc-99m-Sestamibi as a single radiotracer is at least as sensitive in detecting and localizing parathyroid adenomas as TI/Tc-scintigraphy.