Engraftment of bone marrow cells into normal unprepared hosts: effects of 5-fluorouracil and cell cycle status

Bone marrow from animals treated with 5-fluorouracil (5FU) competes equally with normal marrow when assessed in vivo in an irradiated mouse, but shows markedly defective engraftment when transplanted into noncytoablated hosts. Using Southern Blot analysis and a Y-chromosome specific probe, we determined the level of engraftment of male donor cells in the bone marrow, spleen, and thymus of unprepared female hosts. We have confirmed the defective engraftment of marrow harvested 6 days after 5FU (FU-6) and transplanted into unprepared hosts and shown that this defect is transient; by 35 days after 5FU (FU-35), engraftment has returned to levels seen with normal marrow. FU-6 marrow represents an actively cycling population of stem cells, and we hypothesize that the cycle status of the stem cell may relate to its capacity to engraft in the nonirradiated host. Accordingly, we have evaluated the cycle status of engrafting normal and FU-6 marrow into normal hosts using an in vivo hydroxyurea technique. We have shown that those cells engrafting from normal marrow and over 70% of the cells engrafting from FU-6 marrow were quiescent, demonstrating no killing with hydroxyurea. We have also used fluorescent in situ hybridization (FISH) analysis with a Y-chromosome probe and demonstrated that normal and post-5FU engraftment patterns in peripheral blood were similar to those seen in bone marrow, spleen, and thymus. Altogether these data indicate that cells engrafting in normal, unprepared hosts are dormant, and the defect that occurs after 5FU is concomitant with the induction of these cells to transit the cell cycle.     

Subclinical impairment of brain function in chronic hepatitis C infection

BACKGROUND/AIMS: Central nervous system abnormalities such as fatigue and depression occur more frequently in chronic hepatitis C virus (HCV) infection than in many other causes of chronic liver disease. The finding that fatigue is unrelated to activity of hepatitis or mode of infection could indicate an independent effect of HCV on brain function. This study tested the hypothesis of a subclinical cognitive dysfunction in HCV-infected patients. METHODS: One-hundred untreated HCV-RNA positive biopsy-proven patients were investigated by P300 event-related potentials, a sensitive electrophysiologic test of cognitive processing. Health-related quality of life and fatigue were assessed using the SF-36 questionnaire and the Fatigue Impact Scale, respectively. RESULTS: Cognitive brain function was subclinically impaired in the cohort of HCV-infected patients as indicated by significantly prolonged P300 latencies (P=0.01 for comparison to matched healthy subjects) and reduced P300 amplitudes (P<0.001, respectively). Seventeen of the 100 HCV-infected patients had P300 latencies outside the age-adjusted normal range. Abnormal P300 characteristics were not related to the degree of histologic or biochemical activity of hepatitis, severity of fatigue or mental health impairment. CONCLUSIONS: This study demonstrates that patients with HCV infection showed a slight but significant neurocognitive impairment, possibly indicating a further extrahepatic manifestation of chronic hepatitis C.     

Treatment of High Blood Pressure in Germany

The reunification of Germany has made it possible to compare the health care in two independently developed social structures. The prevalence of hypertension was considerably greater in East German men and women, compared with West German men and women, although salt intake was lower in East Germany than in West Germany. Cardiovascular mortality was correspondingly greater. A centralized public health effort was used in East Germany, whereas in West Germany, the activities were decentralized and to a large extent dependent on private philanthropists. In the last two decades, cardiovascular mortality declined in West German men and women, whereas the same was not true for East German men and women. Hypertension incidence, awareness, treatment, and control have improved slightly in Germany, but not enough to explain the improved morbidity figures. Twenty percent of men and women remain unaware of their hypertension, 40% are aware but not treated, and only half are aware and controlled. Complacency is unjustified in Germany and much needs to be done.     

Ablation of Typical Atrial Flutter Using a Three-Dimensional Ultrasound Mapping System

Aims: The aim of the study was to test the feasibility of the new Realtime Position Management mapping system for ablation of typical atrial flutter. Methods and Results: The ultrasound multi-transducer catheters of the RPM Mapping System are placed in the coronary sinus and at the right ventricular apex. Position and movement of the ablation catheter can be depicted on the monitor at any time. Several guiding marks are set in the right atria and thus, define the subsequent lesion lines. A total of 15 patients were treated. In 13 patients complete bi-directional block was established after the ablation. In two patients only significant conduction delay was measured after the end of the procedure. A total of 10.2 ± 6.3 cooled RF-applications were needed to reach the end-point of the procedure. The total energy was 18.76 ± 13.23 J. The fluoroscopy time for ablation was 22.2 ± 8.34 min. During a mean follow-up of 8.4 ± 3.2 months no recurrence of atrial flutter occurred. One patient developed atypical flutter and another patient had atrial fibrillation. Both patients were treated with antiarrhythmic drugs. There was one ablation related complication, a pericardial effusion. Conclusion: The Realtime Position Management system is easy to manage and control. The precision of anatomical linear lesions is improved and fluoroscopic exposure time considerably reduced after learning curve.     

Allogeneic and autologous transplantation for haematological diseases,solid tumours and immune disorders: definitions and current practice in Europe

The Accreditation Sub-Committee of the EBMT regularly publishes special reports on current practice of haemopoietic stem cell transplantation for haematological diseases, solid tumours and immune disorders. Major changes have occurred since the last report in 1998. Haemopoietic stem cell transplantation today includes allogeneic and autologous stem cells derived from bone marrow, peripheral blood and cord blood. With reduced intensity conditioning regimens in allogeneic transplantation, the age limit has increased, permitting the inclusion of older patients. New indications have emerged, such as autoimmune disorders and AL amyloidosis for autologous, and solid tumours for allogeneic transplants. Other indications, such as autologous transplantation for breast cancer have been challenged. An updated report with revised tables and operating definitions is presented here.     

Treatment of acute pulmonary embolism: local effects of three hydrodynamic thrombectomy devices in an ex vivo porcine model.

PURPOSE: To report an ex vivo study on the local effects of hydrodynamic thrombectomy for the treatment of acute pulmonary embolism (off-label use). METHODS: Three devices (6-F AngioJet Xpeedior and 6-F and 8-F Oasis) were used for hydrodynamic thrombectomy inside the arteries of 24 inflated and perfused porcine lung explants. Each system was used at multiple positions inside 4 intact and 4 embolized lungs in vessels measuring 2 to 4 mm, 4 to 6 mm, 6 to 8 mm, and 8 to 10 mm. Angiograms prior to, during, and after catheter positioning and system operation were used to detect arterial wall trauma and to measure local clot removal per 30-second cycle. A total of 21 vessel wall samples were subjected to scanning electron microscopy (SEM) to evaluate non-perforating lesions. RESULTS: All systems were able to remove clot material. The average recanalized vessel length normalized to 30 seconds for vessel diameters of 2 to 4 and 8 to 10 mm, respectively, was 1.17 and 1.75 cm (AngioJet), 0.97 and 0.25 cm (6-F Oasis), and 2.2 and 1.05 cm (8-F Oasis). Perforations occurred during positioning of the 6-F Oasis (4/78 maneuvers) and 8-F Oasis (13/60), but not the AngioJet (0/89); perforations were also seen during system operation (AngioJet: 21/89 activations, 6-F Oasis: 4/78, and 8-F Oasis: 9/60; all lesions inside vessels <6 mm in diameter). SEM showed 35 lesions, 14 with perforation (contrast extravasation) and 21 without perforation (induced by the tip of the guidewire). CONCLUSION: The AngioJet was most efficient in clot removal, followed by the 8-F Oasis. The 6-F Oasis was least efficient, but had fewest complications. According to these experiments, the tested hydrodynamic thrombectomy devices may cause perforations in vessels <6 mm in diameter. Changes in catheter design to reduce system-specific complication rates or to improve the efficacy of clot removal are warranted.     

Subcutaneous panniculitis complicating pancreatic acinar cell carcinoma

Acinar cell carcinoma of the pancreas is rare and can occur with the unusual presentation of arthritis and panniculitis that mimic erythema nodosum. We report a case and review the available literature regarding this rare condition of erythema nodosum and panniculitis associated with bilateral ankle and feet pain, which has rendered the patient virtually wheelchair‐bound.     

Cryocatheter ablation of right ventricular outflow tract tachycardia

INTRODUCTION: Cryocatheter techniques have been successfully applied to treat supraventricular tachycardia but there are no reports on their value in treating ventricular tachycardia (VT). We present our initial experience with cryocatheter ablation of right ventricular outflow tract (RVOT) tachycardia. METHODS AND RESULTS: Cryocatheter ablation was attempted in 14 patients (13 females, age 45.9 +/- 12.7 years) who were highly symptomatic due to frequent monomorphic ventricular extrasystole (VES) or nonsustained VT originating within the RVOT. A 9-Fr, 8-mm-tip cryocatheter was used for both mapping and ablation. Cryoablation was started after localizing the arrhythmic focus by pace and activation mapping. Ablation success, defined by complete disappearance of target VES/VT acutely and during a follow-up of 9.3 +/- 1.4 weeks, was achieved in 13 of 14 patients. Ablation was successful with local activation times of 35 +/- 4 ms, 5.8 +/- 3.3 applications, 18.8 +/- 7.5 minutes total cryo time, 9.4 +/- 4.2 minutes fluoroscopy time, and 66.9 +/- 26.1 minutes total procedure time, the latter two measures showing a reduction with number of patients treated. Three patients reported slight pain related to local pressure of the catheter on the RVOT wall. No pain was described related to delivery of cryothermal energy. CONCLUSIONS: Initial experience shows that focal VES/VT originating in the RVOT can be successfully treated using cryocatheter ablation. Acute and short term success rates, fluoroscopy times, and duration of procedure are comparable to conventional ablation techniques. A major advantage seems to be the virtual absence of ablation related pain.     

Specific anti-marmoset T-cell globulin: Cytotoxic and mitogenic properties

Summary A virus-transformed marmoset lymphoblastoid cell line (LCL) with T-cell characteristics was used for the production of rabbit anti-marmoset T-cell globulin (RAMTG). Exhaustive absorption of the crude antiserum with kidneyliver homogenate and pooled marmoset B-LCL yielded a T-cell-specific antibody. Specificity of the absorbed RAMTG was evidenced by plateau formation in the cytotoxic activity on marmoset peripheral blood lymphocytes (PBL) and clear discrimination between marmoset T-LCL and B-LCL. Unexpectedly, the absorbed RAMTG was not cytotoxic for human PBL.Assays for mitogenic activity showed that unabsorbed RAMTG exhibited mitogenic activity on marmoset, but not on human or baboon PBL. Unabsorbed rabbit anti-human T-cell globulin (RAHTG) induced cellular proliferation in human and baboon PBL, whereas marmoset orSaimiri sciureus PBL showed no response. Absorbed RAMTG did not stimulate DNA synthesis of marmoset PBL.In conclusion, the specific RAMTG may be useful for studies on the functional role of T-lymphocytes in the marmoset immune response to organ allografts or infectious agents.This work was supported by Deutsche Forschungsgemeinschaft, SFB 37, E3, E10, and G7