Autologous stem cell transplantation following simultaneous liver and kidney transplantation in severe amyloid light chain amyloidosis associated with multiple myeloma: a case report.

INTRODUCTION: The involvement of vital organs in multiple myeloma (MM) with systemic amyloid light-chain (AL) amyloidosis can lead to acute organ failure. In this case, the fear of recurrence or progression of multiple myeloma often excludes those patients from undergoing organ transplantation. Nevertheless, clinically fit patients might benefit from a different therapeutic approach. This case presentation might highlight this particular unmet need and strengthen a different treatment approach. CASE PRESENTATION: To our knowledge, we present the first case of successful simultaneous liver and kidney transplantation, followed by autologous stem cell transplantation in a 60-year-old Caucasian male patient suffering from MM (Durie-Salmon stage IIB; ISS-stage: III, RISS stage: III) with primary AL amyloidosis. Chemotherapy treatment led to end-stage kidney disease requiring dialysis. Liver failure also occurred after at least three cycles of CyBorD (bortezomib, cyclophosphamide, and dexamethasone) of induction therapy with a good hematologic response. Over three years after the initial diagnosis, the patient is reportedly showing an excellent quality of life and a complete remission. DISCUSSION AND CONCLUSION: We conclude that kidney and liver transplantation followed by autologous stem cell transplantation can be a treatment option for a selected group of patients with MM if AL amyloidosis is leading. In the end, the remission assessment by IMWG response criteria displayed a complete remission of MM together with complete reconstitution of organ functions (liver & renal function) as long as upfront clinical evaluation excludes significant cardiac involvement and other severe co-morbidities.

Interferon-free regimens improve portal hypertension and histological necroinflammation in HIV/HCV patients with advanced liver disease.

BACKGROUND: HIV/HCV co-infected patients show accelerated fibrosis progression and higher risk for complications of portal hypertension (PHT). AIM: To assess the effects of interferon-free therapy on portal pressure, liver histology and plasma biomarkers in HIV/HCV-coinfected patients with PHT. METHODS: Twenty-two patients with paired hepatic venous pressure gradient (HVPG) measurements prior and after successful treatment (SVR) with interferon-free regimens were included. Liver stiffness was assessed by transient elastography and biopsies were scored according to METAVIR. Plasma biomarkers were determined by ELISA. RESULTS: Overall, HVPG decreased from 10.7 ± 4.1 mmHg at baseline to 7.4 ± 4.2 mmHg after HCV treatment (Δ:-3.3 ± 2.7 mmHg; p < 0.001). In patients with clinically significant PHT (HVPG≥10 mmHg, n = 11), HVPG decreased from 14.1 ± 2.9 to 10.4 ± 3.9 mmHg (Δ:-3.7 ± 3.3 mmHg; p = 0.004) and a haemodynamic response (HVPG decrease ≥10%) was observed in 73%. In 64% of patients with subclinical PHT (HVPG 6-9 mmHg, n = 11), portal pressure normalised at SVR. Mean liver stiffness decreased from 20.8 kPa to 11.5 kPa (Δ:-8.8 ± 7.4 kPa; p < 0.001). Fifty percent (7/14) of patients with cirrhosis were re-classified as METAVIR ≤F3 and all patients with decompensated cirrhosis improved their Child-Pugh stage. After successful HCV treatment, 39% still had persistent histological necroinflammatory activity (METAVIR A1), which correlated with less HVPG response and more steatosis. While most biomarkers improved with SVR, METAVIR A1 patients had significantly higher plasma levels of fibrogenic (PDGF, TGF-ß) and angiogenic (VEGF, Angiopoietin1) biomarkers. CONCLUSIONS: Interferon-free therapy reduces PHT and halts histological necroinflammatory activity in the majority of HIV/HCV-coinfected patients after SVR, which may lead to re-compensation of liver function in cirrhosis. Biomarkers could identify patients with persisting hepatic necroinflammation.

Overexpression of hypoxia-inducible factor 1alpha is a marker for an unfavorable prognosis in early-stage invasive cervical cancer.

Hypoxia-inducible factor 1alpha (HIF-1alpha) is a transcriptional factor that regulates genes involved in response to hypoxia and promotes neoangiogenesis, which are considered essential for tumor growth and progression. Using immunohistochemistry, we investigated the influence of HIF-1alpha expression on prognosis in 91 patients with cervical cancer stage pT1b. In univariate and multivariate analysis, patients with strong expression of HIF-1alpha had a significantly shorter overall survival time (P = 0.0307, log-rank test) and disease-free survival time (P < 0.0001, log-rank test) compared with those with moderate to absent HIF-1alpha expression. HIF-1alpha expression is a strong independent prognostic marker in early stage cervical cancer.

Overexpression of Id-1 protein is a marker for unfavorable prognosis in early-stage cervical cancer.

Inhibitor of differentiation/DNA binding (Id) proteins are transcription factors, involved in cell cycle regulation and neoangiogenesis. Using immunohistochemistry, we investigated the prognostic influence of Id-1, Id-2, and Id-3 expression in 89 patients with cervical cancer stage pT(1b). In univariate and multivariate analysis, patients with strong or moderate expression of Id-1 had a significant shorter overall survival time (P = 0.0144, log-rank test) and disease-free survival time (P = 0.0107, log-rank test) compared with those with low or absent Id-1 expression. Id-1 expression is an independent prognostic marker in early-stage cervical cancer.

Benzamide riboside induces apoptosis independent of Cdc25A expression in human ovarian carcinoma N.1 cells.

One of the mechanisms of action of a new oncolytic agent, benzamide riboside (BR) is by inhibiting inosine 5'-monophosphate dehydrogenase (IMPDH) which catalyzes the formation of xanthine 5'-monophosphate from inosine 5'-monophosphate and nicotinamide adenine dinucleotide, thereby restricting the biosynthesis of guanylates. In the present study BR (10 - 20 microM) induced apoptosis in a human ovarian carcinoma N.1 cell line (a monoclonal derivative of its heterogenous parent line HOC-7). This was ascertained by DNA fragmentation, TUNEL assay, [poly(ADP)ribose polymerase]-cleavage and alteration in cell morphology. Apoptosis was accompanied by sustained c-Myc expression, concurrent down-regulation of cdc25A mRNA and protein, and by inhibition of Cdk2 activity. Both Cdk2 and cdc25A are G1 phase specific genes and Cdk2 is the target of Cdc25A. These studies demonstrate that BR exhibits dual mechanisms of action, first by inhibiting IMPDH, and second by inducing apoptosis, which is associated with repression of components of the cell cycle that are downstream of constitutive c-Myc expression.

Expression of hypoxia-inducible factor 1alpha in epithelial ovarian tumors: its impact on prognosis and on response to chemotherapy.

PURPOSE: To investigate the impact of expression of hypoxia-inducible factor (HIF)-1alpha on prognosis and on response to chemotherapy in epithelial ovarian tumors. EXPERIMENTAL DESIGN: Expression of HIF-1alpha protein was studied by immunohistochemistry in 102 specimens of epithelial ovarian cancers, in 50 borderline tumors, and in 20 cystadenomas. Results were correlated with p53, p21, and bcl-2 expression, microvessel density (MVD), apoptotic rate of tumor cells, and survival. RESULTS: In 68.6% of ovarian cancers and 88% of borderline tumors, expression of HIF-1alpha was observed. There was a significant correlation of HIF-1alpha protein expression and MVD (P < 0.001). HIF-1alpha overexpression alone and MVD showed no impact on survival of cancer patients. Furthermore, the response to platinum-based chemotherapy was independent from HIF-1alpha expression. Expression of HIF-1alpha correlated with apoptotic rate in the majority of cases, especially in low malignant potential tumors. In contrast, in cancer patients with strong expression of HIF-1alpha and p53 protein overexpression, not only a significantly increased MVD (P = 0.032, Mann-Whitney test) but also a significantly shorter overall survival was observed (P < 0.0001, Cox regression). The apoptotic rate was very low in these tumors. CONCLUSIONS: HIF-1alpha protein overexpression alone has no impact on the prognosis of ovarian cancer. The combination of HIF-1alpha protein overexpression with nonfunctional p53, however, indicates a dismal prognosis.

Selective immunohistochemical staining of blood and lymphatic vessels reveals independent prognostic influence of blood and lymphatic vessel invasion in early-stage cervical cancer.

Lymphovascular space invasion was shown to play a key role in the progression of cervical cancer. Because of the absence of a specific marker for lymphatic vessels, earlier studies could not reliably distinguish between blood and lymphatic vessel invasion. By immunostaining for podoplanin, a novel marker for lymphatic endothelium, and for factor VIII-related antigen, we determined lymphatic and blood vessel invasion in tissue samples of 98 patients with cervical cancer pT1b treated by radical hysterectomy. Eleven (11.2%) specimens showed invasion of blood vessels, 20 (20.4%) showed invasion of lymphatic vessels, and 15 (15.3%) showed invasion of blood and lymphatic vessels. There was a strong association of lymphatic vessel invasion and lymph node involvement (P < 0.001). In univariate analysis, both blood and lymphatic vessel invasion failed to reach a statistically significant influence on overall survival, but a significant influence on disease-free survival was found (P = 0.0002 and P < 0.0001, respectively). In multivariate analysis of disease-free survival, only blood vessel invasion remained statistically significant (P = 0.0457). Lymphatic vessel invasion reached significance when lymph node status was excluded from the model (P = 0.0025). Both lymphatic vessel and blood vessel invasion occur frequently in early-stage cervical cancer. Determination of the vessel status may be of clinical importance because it signifies the risk of recurrent disease.

Evaluation of the United States Food and Drug Administration-approved scoring and test system of HER-2 protein expression in breast cancer.

PURPOSE: The purpose of this study was to investigate the prognostic significance of assessment of human epidermal growth factor receptor (HER)-2 oncogene protein overexpression of breast cancer tissue by the United States Food and Drug Administration (FDA)-approved HercepTest and grading system (negative, 0 or 1+; weakly positive, 2+; strongly positive, 3+). Furthermore, results of the HercepTest were correlated with immunohistochemical results obtained using different antibodies and protocols and with HER-2 oncogene gene amplification assessed by fluorescence in situ hybridization (FISH). EXPERIMENTAL DESIGN: HER-2 status in 303 patients with lymph node-positive breast cancer was investigated by using a rabbit polyclonal antibody (DAKO) by conventional immunohistochemistry and by applying the HercepTest. Furthermore, the monoclonal antibody CB-11 was used in conventional immunohistochemistry and with the NexES automatic stainer, which is also under consideration for FDA approval for determination of eligibility for Herceptin therapy. Results were compared with FISH analysis performed in all 2+ and 3+ specimens (103 cases) and 104 HER-2-negative specimens. RESULTS: 3+ positive carcinomas were found in 8.9-15.7% of specimens. FISH revealed that almost exclusively 3+ positive cases were amplified, with the HercepTest and the NexES automatic stainer giving the best results. In univariate analysis, staining with the HercepTest revealed a significantly worse prognosis in 3+ cases. Also, 3+ cases were significantly associated with lower estrogen receptor levels and histological grade III tumors. CONCLUSIONS: This study shows that the results of the FDA-approved HER-2 grading and test system correlated strongly with findings in FISH. Furthermore, HercepTest proved to be of prognostic relevance. Strict adherence to the given protocols is critical.

High proportion of granzyme B-positive (activated) intraepithelial and lamina propria lymphocytes in lymphocytic gastritis.

Intraepithelial lymphocytes (IELs) and lamina propria lymphocytes (LpLs) have not been well studied in gastric mucosa, particularly in lymphocytic gastritis. Therefore, they were immunohistologically characterized with antibodies recognizing CD3, CD8, CD57, T cell-restricted intracellular antigen (TIA-1), and granzyme B (GrB). The TIA-1 labels cytotoxic granules of resting and activated T-cells, whereas GrB decorates activated cytotoxic T cells. Thirty patients with celiac disease, including 20 taking gluten and 10 on a gluten-free diet, 15 patients with nonceliac disease-associated lymphocytic gastritis, and 20 controls were studied. Stained cells were counted and results were given as IELs/100 epithelial cells or percentage of lamina propria cells. Sixty percent to 90% of CD3+ IELs and up to 12% of lamina propria cells contained TIA-1-positive cytotoxic granules. The number of GrB+ IELs and LpLs was increased in Helicobacter pylori-positive controls (p < 0.03 vs. H pylori-negative controls) and celiac disease patients taking gluten (p < 0.05 vs. controls). The highest number of GrB+ IELs and LpLs was found in nonceliac disease-associated lymphocytic gastritis (p < 0.009 vs. controls, p < 0.05 vs. celiac disease). This study shows that a high proportion of gastric IELs and LpLs is potentially cytotoxic in nature. Through stimuli not yet identified, a proportion of them becomes activated after H pylori infestation and in lymphocytic gastritis.

Aberrant esophageal HLA-DR expression in a high percentage of patients with Crohn's disease.

Esophageal histology is not well studied in patients with Crohn's disease (CD). We, therefore, analyzed the histologic and immunohistologic appearance of esophageal mucosa in CD. Biopsy specimens taken from the esophagus of 57 consecutive patients with known CD of the large and/or small bowel, of 200 Crohn's-free controls, of 15 cases with ulcerative colitis, and of 5 cases with viral esophagitis were evaluated. In controls, most patients had either HLA-DR negative esophageal epithelium or showed focal or diffuse basal staining. HLA-DR expression of all epithelial layers (transepithelial staining) was observed in only four (2%) control subjects, in one case with herpes esophagitis, but not in patients with ulcerative colitis. In contrast, transepithelial HLA-DR expression was found in 19 (33%) patients with CD (p < 0.0001). In CD patients, it was associated with a significantly increased epithelial content in T-cells (CD3+, TIA-1+, granzyme B+), B-cells (CD79a+), natural killer cells (CD57+), and macrophages (CD68+). There was no correlation with either histological findings elsewhere in the upper gastrointestinal tract or with laboratory findings, symptoms, CDAI, or medication. Transepithelial esophageal HLA-DR expression is common in CD. Immunohistochemistry may prove useful in supporting the histologic diagnosis of CD in staging procedures, for initial diagnosis as well as in doubtful cases.

Endogenous interleukin 1 receptor antagonist during human bone marrow transplantation: increased levels during graft-versus-host disease, during infectious complications, and after immunoglobulin therapy.

In order to understand in more detail the role of endogenous interleukin 1 receptor antagonist (IL-1ra) during bone marrow transplantation, IL-1ra serum levels of 28 patients undergoing allogeneic (n=25) or autologous (n=3) bone marrow transplantation were measured with a commercially available ELISA. In addition, the impact of intravenous immunoglobulin (IVIG) was evaluated by analyzing IL-1ra serum levels before and 2, 5, and 24 hr after IVIG infusion. IL-1ra measurements revealed a nadir of circulating IL-1ra levels 3-5 days after bone marrow transplantation, with an increase during conditioning and hematological reconstitution. Circulating IL-1ra levels were significantly increased in patients with cytomegalovirus (CMV) disease, CMV reactivation, graft-versus-host disease (GVHD), or fever of unknown origin, when compared with time-matched controls without complications. Highest levels were observed in patients with CMV disease (1922+/-388 pg/ml), followed by patients with CMV reactivation (1575+/-435 pg/ml) and GVHD (1178+/-317 pg/ml). The magnitude of IL-1ra increase in GVHD was related to disease severity. Patients with grade III-IV GVHD developed higher IL-1ra levels than did patients with grade I-II GVHD. Lower but still significantly elevated IL-1ra levels were observed during fever of unknown origin (384+/-87 pg/ml). An increase of IL-1ra serum levels followed the administration of IVIG before transplantation and after hematopoietic reconstitution, but not during aplasia, pointing to the important role of hematopoietic cells in the production of IL-1ra. In conclusion, we show that IL-1ra release is related to conditioning regimen, hematopoietic reconstitution, complications of infectious and alloimmune etiology after bone marrow transplantation, and exogenously administered IVIG.

Impact of human papillomavirus infection on the expression of the KAI1 metastasis suppressor protein in invasive cervical cancer.

Downregulation of KAI1 metastasis suppressor protein is associated with dismal prognosis in a variety of cancers. Mutation of p53 was suggested to be involved in KAI1-downregulation. In cervical cancer, p53 is inactivated by human papillomavirus (HPV) oncoprotein E6 with the grade of inactivation depending on the HPV type. KAI1-expression was immunohistochemically determined in 67 specimens of cervical cancer, HPV-typing was performed using polymerase chain reaction (PCR), cloning, and sequencing. KAI1-downregulation was found in 68.1% of patients, HPV-infection in 91%. There was no association of KAI1-downregulation and infection with a particular HPV type. KAI1-downregulation in cervical cancer seems independent of HPV-E6 induced p53 inactivation.

DNA repair-redox enzyme apurinic endonuclease in cervical cancer: evaluation of redox control of HIF-1alpha and prognostic significance.

The multifunctional apurinic/apyrimidinic endonuclease (Ape1/ref-1) plays a key role in the human DNA base excision repair pathway. Ape1/ref-1 has also been shown to be involved in the redox control of transactivation activities of hypoxia-inducible factor (HIF)-1alpha. The aim of our study was to investigate the expression of these proteins in early stage invasive cervical cancer. Expression of Ape1/ref-1 and HIF-1alpha was detected immunohistochemically in 88 samples of cervical cancer stage pT1b. The levels of the proteins were compared and the prognostic influence of Ape1/ref-1 expression was investigated. Strong nuclear expression of Ape1/ref-1 was observed in 9 cases (10.2%), moderate in 22 cases (25%), weak in 17 cases (19.3%), and absent in 40 cases (45.5%). Furthermore, no correlation between Ape1/ref-1 and HIF-1alpha expression was observed (p=0.864). We also found no relationship of Ape1/ref-1 expression and survival (p>0.05, log-rank test). From these studies, we have concluded that in cervical cancer there is no correlation between the upstream redox regulatory protein of HIF-1, i.e., Ape1/ref-1, and HIF-1alpha expression. However, these studies do not address any functional relationship between the two proteins.

Prognostic relevance of three histological grading methods in breast cancer.

Histological grading is an important parameter for the risk assessment in patients with breast cancer. However, up to now differing grading methods are used which have not been compared with respect to their prognostic significance. In the present study the prognostic significance of three different methods of histological grading (Elston, Contesso, Helpap) was determined in a sample of 292 patients. Furthermore, results obtained in needle biopsies were compared with those obtained in surgical resection specimens in 31 cases. The mitotic counts and the Contesso method were performed on two microscopes with different field areas (0.238 mm2 and 0.345 mm2). Univariate and multivariate analysis revealed that all three histological grading methods had a high prognostic value concerning overall survival (OS) and disease-free survival (DFS). Using univariate and multivariate analysis the Elston method performed best to determine OS and DFS (p<0.0001 and p<0.001). The field area of the microscope had a minor influence on the mitotic count and on the results of the Contesso method. The histological grading was reliable in needle biopsies: the best agreement to grading obtained in the definitive surgical specimen was achieved with the Elston method (kappa statistic 0.727). As a conclusion, we could show that determination of the histological grade is an important prognostic factor in breast cancer with the Elston method giving the best results. Also, we could demonstrate that histological grading in needle biopsies is reliable enough to allow a preoperative risk estimation.

CD4 monoclonal antibody VIT4 in human alloimmune response in vitro and in vivo.

In the present report the immunosuppressive effects of the murine anti-human CD4 monoclonal antibody (mAb) VIT4 on human alloimmune response in vitro were analyzed. Moreover, the antibody was tested for its activity to prolong allograft survival in seven patients with steroid-refractory allograft rejection. VIT4 inhibited the proliferative response to alloantigens in the mixed lymphocyte reaction (MLR) in a dose-dependent manner. At concentrations of 1 and 10 micrograms/ml VIT4 blocked MLR by 55 +/- 11% and 77 +/- 1%, respectively. Also alloantigen-specific proliferation of in vitro- generated memory T cells was dose-dependently reduced to 23 +/- 1% at a VIT4 concentration of 100 micrograms/ml. Furthermore, at the same dose level VIT4 blocked proliferation of antigen-specific short-term alloreactive CD4+ cell lines and significantly inhibited the in vitro generation of cytotoxic T lymphocytes (CTL). In a pilot study VIT4 (5 mg/d i.v.) was administered to 7 patients with steroid-refractory allograft rejection for 14 days. In 4 of 7 patients graft function transiently improved and graft survival in all patients was prolonged to a mean of 694 days (range 128-2163) from the beginning of the VIT4 treatment. In the light of our in vitro results and the preliminary clinical data, further clinical trials using higher antibody doses are greatly warranted to assess the efficacy of anti-CD4 mAb VIT4 in the treatment of allograft rejection.

In vivo and in vitro permeability in coeliac disease.

BACKGROUND: An increased permeability to sugars is found in the intestine of untreated patients with coeliac disease after oral ingestion. AIM: To test whether in vitro permeability resembles in vivo permeability tests and whether an in vitro gliadin gluten challenge could be performed by an in vitro permeability test. METHODS: We measured in vivo (urinary excretion after sucrose-lactulose-mannitol ingestion) and in vitro permeability (by mini-Ussing chambers) in 25 healthy controls, 12 relatives of coeliac disease patients, 19 treated, eight partly treated and 16 untreated patients with coeliac disease. RESULTS: In vivo sugar permeability was increased in nearly all coeliac patients. Additionally, in vitro permeability to lactulose (P=0.0007), mannitol (P=0.004) and sucrose (P=0.042) was higher in untreated patients with coeliac disease. It correlated with in vivo permeability (sucrose tau=0.61, P=0.006; lactulose tau=0.41, P < 0.0001; mannitol tau=- 0.56, P=0.62) and was dependent on mucosal damage. An in vitro gliadin challenge over 24 h could not significantly change in vitro permeability in treated patients with coeliac disease. CONCLUSIONS: An in vitro permeability test capable of measuring elevated permeability in coeliac mucosa was described, but this test cannot replace oral gluten challenge by in vitro gliadin incubation.

Famotidine versus omeprazole in combination with clarithromycin and metronidazole for eradication of Helicobacter pylori--a randomized, controlled trial.

BACKGROUND: One-week low-dose triple therapy is currently considered the gold standard regimen for treatment of Helicobacter pylori infection. However, the mechanisms involved in the synergy between antibiotics and proton pump inhibitors are controversial. AIMS: To test the hypothesis that acid suppression represents the crucial mechanism by which the antibacterial activity of antibiotics can be enhanced, and to assess the impact of primary resistance on treatment outcome. METHODS: One hundred and twenty patients with H. pylori infection and duodenal ulcer, gastric ulcer or non-ulcer dyspepsia were randomly assigned to a 1 week course of either famotidine 80 mg b.d., clarithromycin 250 mg b.d. and metronidazole 500 mg b.d. (FCM group; n = 60) or omeprazole 20 mg o.d., clarithromycin 250 mg b.d. and metronidazole 500 mg b.d. (OCM group; n = 60). Gastroscopy was performed at baseline and 5 weeks after completion of treatment. H. pylori status was assessed by biopsy urease test, histology and culture. RESULTS: In the intention-to-treat analysis, eradication of H. pylori was achieved in 47 of 60 patients (78%; 95% CI: 66-88%) in the FCM group, compared to 44 of 60 patients (73%; 95% CI: 60-84%) in the OCM group (N.S.). Using per protocol analysis, eradication therapy was successful in 47 of 52 patients (90%; 95% CI: 79-97%) treated with FCM and 44 of 57 patients (77%; 95% CI: 64-87%) treated with OCM (N.S.). Primary metronidazole resistance was present in 27% and primary clarithromycin resistance in 8% of strains. Overall per protocol eradication rates in strains susceptible to both antibiotics and strains with isolated metronidazole resistance were 93% and 84%, respectively. No patient with clarithromycin resistance responded to treatment. CONCLUSIONS: High-dose famotidine and omeprazole, combined with clarithromycin and metronidazole, are equally effective for eradication of H. pylori. In 1-week low-dose triple therapy, metronidazole resistance has no major impact on eradication rates whereas clarithromycin resistance is associated with a poor treatment outcome.

Efficacy of thrombolytic therapy in pulmonary embolism determined by MION-enhanced MRA: an experimental study in rabbits.

RATIONALE AND OBJECTIVES: This study determined whether contrast-enhanced magnetic resonance angiography could be used as a noninvasive imaging technique to determine the therapeutic effect and endpoint in thrombolysis of acute pulmonary embolism in an animal model. METHODS: New Zealand white rabbits (n = 18) were anesthetized and mechanically ventilated. Single (n = 12 emboli) or dual (n = 12 emboli in 6 animals) pulmonary emboli were created by injecting autologous thrombi through a right internal jugular venous approach. Three-dimensional time of flight (TOF) magnetic resonance angiograms were obtained after intravenous administration of 2 mg Fe of a long circulating monocrystalline iron oxide. Animals then received 5000 IU heparin and 1.3 mg recombinant tissue plasminogen activator/kg intravenously, and magnetic resonance angiography was repeated 30 minutes and 60 minutes after initiation of thrombolytic therapy. RESULTS: MION-enhanced magnetic resonance angiography accurately detected pulmonary emboli in all rabbits. Thrombolysis during the observation period was successful in 8 of the 18 animals. In animals with a single embolus, the revascularization rate was 50% (6 of 12 emboli). The rate was 33% (4 of 12 emboli) in animals with multiple emboli. Magnetic resonance angiography allowed determination of thrombus resolution or thrombus persistence. CONCLUSIONS: It was feasible to diagnose pulmonary embolism accurately in this experimental study and to monitor thrombolysis of pulmonary emboli by MION-enhanced magnetic resonance angiography.

Gastrointestinal perforation early after peripheral blood stem cell transplantation for AL amyloidosis.

The morbidity and mortality of AL amyloidosis is caused by the deposition of Ig light chains as amyloid protein in vital organs. With conventional therapy median survival of patients with AL amyloidosis is 10-14 months. With high-dose chemotherapy clinical remissions of organ-specific disease have been reported. Here, we present a patient with high-risk AL amyloidosis who was given high-dose therapy and a peripheral blood stem cell transplant. Four days later she died of gastrointestinal perforation due to amyloid infiltrations.

Pneumatosis [correction of Pneumocystis] cystoides intestinalis with pneumoperitoneum and pneumoretroperitoneum in a patient with extensive chronic graft-versus-host disease.

Pneumatosis cystoides intestinalis is a rare finding of intramural gasfilled cysts in the bowel wall and sometimes free air in the abdomen. A few conditions are reported to cause this disease, one of them being immunosuppression. We describe a 50-year-old Caucasian male with extensive chronic graft-versus-host disease (GVHD) of the gut and skin who developed PCI with pneumoperitoneum and pneumoretroperitoneum. To our knowledge, this is the first report of PCI occurring in a patient with active chronic GVHD which resolved spontaneously.