Progenitor cell recruitment during individualized high-flow, very-large-volume apheresis for autologous transplantation improves collection efficiency

BACKGROUND: Individual adaptation of processed patient's blood volume (PBV) should reduce number and/or duration of autologous peripheral blood progenitor cell (PBPC) collections. STUDY DESIGN AND METHODS: The durations of leukapheresis procedures were adapted by means of an interim analysis of harvested CD34+ cells to obtain the intended yield of CD34+ within as few and/or short as possible leukapheresis procedures. Absolute efficiency (AE; CD34+/kg body weight) and relative efficiency (RE; total CD34+ yield of single apheresis/total number of preapheresis CD34+) were calculated, assuming an intraapheresis recruitment if RE was greater than 1, and a yield prediction models for adults was generated. RESULTS: A total of 196 adults required a total of 266 PBPC collections. The median AE was 7.99 x 10(6), and the median RE was 1.76. The prediction model for AE showed a satisfactory predictive value for preapheresis CD34+ only. The prediction model for RE also showed a low predictive value (R2 = 0.36). Twenty-eight children underwent 44 PBPC collections. The median AE was 12.13 x 10(6), and the median RE was 1.62. Major complications comprised bleeding episodes related to central venous catheters (n = 4) and severe thrombocytopenia of less than 10 x 10(9) per L (n = 16). CONCLUSION: A CD34+ interim analysis is a suitable tool for individual adaptation of the duration of leukapheresis. During leukapheresis, a substantial recruitment of CD34+ was observed, resulting in a RE of greater than 1 in more than 75 percent of patients. The upper limit of processed PBV showing an intraapheresis CD34+ recruitment is higher than in a standard large-volume leukapheresis. Therefore, a reduction of individually needed PBPC collections by means of a further escalation of the processed PBV seems possible.

Mechanisms of airway obliteration after lung transplantation

Post-transplant bronchiolitis obliterans, also called bronchiolitis obliterans syndrome, affects up to 50-60% of patients who survive 5 yr after surgery according to its clinical definition, which is based on the degree of obstructive airway disease. Alloimmune-independent and -dependent mechanisms produce injuries and inflammation of epithelial cells and subepithelial structures, leading to aberrant tissue repair. The triggering of innate immunity by various infections or chemical injuries after, for example, gastroesophageal reflux, may lead to the release of danger signals that are able to activate dendritic cells, a crucial link with adaptive immunity. Inflammation can also increase the expression and display of major histocompatibility alloantigens and thus favor the initiation of rejection episodes. These phenomena may be limited in time and location or may be protracted. Reducing the risk of alloimmune-independent factors may be as important as treating acute episodes of lung rejection. Excessive immunosuppression may be deleterious by increasing the risk of infection, thereby triggering innate and adaptive immunity. New potential therapeutic targets are emerging from the research performed on leukotriene receptors, chemokine receptors, and growth factors. Neutralizing these molecules reduces the initial mononuclear and polynuclear infiltrates or the subsequent fibroproliferative process and the neovascular changes, feeding this process.

ABO histo-blood group antigen expression on the graft endothelium long term after ABO-compatible, non-identical heart transplantation

We recently reported a complete change in the endothelial ABO histo-blood group phenotype of a cardiac allograft long term after B to O mismatched transplantation. In the context of the current controversy on graft recolonization with recipient endothelial cells and its importance in the development of immunological unresponsiveness, we monitored the expression of endothelial ABH histo-blood group antigens of 10 ABO-compatible, non-identical cardiac allografts over an observation period of at least 30 months. ABH antigens as well as markers for endothelial cells, erythrocytes and thrombocytes were investigated retrospectively by immunohistochemistry using monoclonal antibodies on sections of formalin-fixed, paraffin-embedded biopsies and were evaluated semi-quantitatively by microscopy. In contrast to our earlier finding of the change in the endothelial ABO histo-blood group phenotype long term after ABO- mismatched transplantation, we could not confirm this change in 10 compatible but non-identical cases.

[Tooth extraction under medication with acetylsalicylic acid.]

PURPOSE: The purpose of this prospective study was to show and analyze the bleeding complications after teeth extraction under therapy with 100 mg acetylsalicylic acid (ASA) and to compare them to bleeding complications after teeth extraction in patients with a healthy blood profile.PATIENTS AND METHODS: In 65 patients under medication with 100 mg ASA and in 252 healthy patients, 151/ 543 teeth were extracted and the bleeding complications monitored.RESULTS: The postoperative bleeding frequency was 1.54% in the ASA 100 group and 1.59% in the healthy control group without any medication. No serious or uncontrollable postoperative bleedings arose in either group. All bleedings could be easily handled. No obvious difference concerning the bleeding frequency between the two groups was observed. The small number of bleeding events and the complexity of affecting parameters did not permit statistical tests.CONCLUSION: It is not necessary to interrupt the medication of 100 mg acetylsalicylic acid given to prevent thromboembolism before tooth extractions.

Successful kidney transplantation from donor with Marfan's syndrome

Marfan's syndrome is caused by mutations in the extracellular matrix protein fibrillin-1 with aortic aneurysm and dissection being its most life-threatening manifestations. Kidney transplantation from donors with Marfan's syndrome has never been reported in the literature, possibly because of reticences due to the underlying connective tissue disease. Here, we report two patients with end-stage renal disease, transplanted with the kidneys from a donor with Marfan's syndrome who died of aortic dissection and cerebral hemorrhage. After delayed graft function in both recipients, renal function normalized with no renovascular complications and negative proteinuria for 6 years in one patient and 2 years in the other patient, who died from an ischemic cerebrovascular insult. Kidneys from organ donors with Marfan's syndrome might be suitable for transplantation.

Metzincins, including matrix metalloproteinases and meprin, in kidney transplantation

Chronic allograft nephropathy, including chronic rejection, remains one of the major causes of renal allograft failure. Amongst other mediators, metzincins, such as matrix metalloproteinases (MMP), direct extracellular matrix metabolism and cell proliferation. Thus, we hypothesized, that these proteolytic enzymes are differentially regulated in chronic renal transplant rejection in rats and in human renal allograft nephropathy. Our studies demonstrated on the experimental level and in humans an overall up-regulation of MMP, tissue inhibitors of metalloproteinases (TIMP) and related enzymes as a result of rejection processes. Thus, metzincins may represent novel markers and therapeutic targets with respect to renal allograft rejection.

High-dose therapy and autologous stem cell transplantation for children with HIV-associated non-Hodgkin lymphoma

In contrast to adults, autologous stem cell transplantation (ASCT) as part of the salvage strategy after high-dose chemo/radiotherapy in human immunodeficiency virus (HIV) related Non-Hodgkin lymphoma (NHL) is not yet established for children. We report on a 13-year patient with congenital HIV infection and refractory Burkitt lymphoma, who was successfully treated by high-dose therapy (HDT) including rituximab followed by ASCT. After 26 months follow-up the patient remains in complete remission and his HIV parameters have normalized with continued highly active antiretroviral therapy (HAART). HIV infection may no longer exclude children from ASCT as part of salvage therapy. Pediatr Blood Cancer (c) 2006 Wiley-Liss, Inc.

Haematopoietic stem cell transplantation in Switzerland. Report from the Swiss Transplant Working Group Blood and Marrow Transplantation (STABMT) Registry 1997-2003

In 1997, the Swiss Transplant Working Group Blood and Marrow Transplantation (STABMT) initiated a mandatory national registry for all haematopoietic stem cell transplants (HSCT) in Switzerland. As of 2003, information was collected of 2010 patients with a first HSCT (577 allogeneic (29%) and 1433 autologous (71%) HSCT) and 616 additional re-transplants. This included 1167 male and 843 female patients with a median age of 42.4 years (range 0.2-76.6 years). Main indications were leukaemias (592; 29%) lymphoproliferative disorders (1,061; 53%), solid tumours (295; 15%) and non-malignant disorders (62; 3%). At the time of analysis 1,263 patients were alive (63%), 747 had died (37%). Probability of survival, transplant related mortality or relapse at 5 years was 52%, 21%, 36% for allogeneic and 54%, 5%, 60% for autologous HSCT. Outcome depended on indication, donor type, stem cell source and age of patient. HSCT is an established therapy in Switzerland. These data describe current practice and outcome.

Clinical evaluation of 3 overdenture concepts with tooth roots and implants: 2-year results

PURPOSE: In the present cohort study, overdentures with a combined root and implant support were evaluated and compared with either exclusively root- or implant-supported overdentures. Results of a 2-year follow-up period are reported, namely survival of implants, root copings, and prostheses, plus prosthetic complications, maintenance service, and patient satisfaction. MATERIALS AND METHODS: Fourteen patients were selected for the combined overdenture therapy and were compared with 2 patient groups in which either roots or implants provided overdenture support. Altogether, 14, 17, and 15 patients (in groups 1, 2, and 3, respectively) were matched with regard to age, sex, treatment time, and observation period. The mean age was around 67 years. Periodontal parameters were recorded, radiographs were taken, and all complications and failures were registered during the entire observation time. The patients answered a 9-item questionnaire by means of a visual analogue scale (VAS). RESULTS: One implant failed and 1 tooth root was removed following longitudinal root fracture. Periodontal/peri-implant parameters gave evidence of good oral hygiene for roots and implants, and slight crestal bone resorption was measured for both. Technical complications and service performed were significantly higher in the first year (P < .04) in all 3 groups and significantly higher in the tooth root group (P < .03). The results of the VAS indicated significantly lower scores for satisfaction, speaking ability, wearing comfort, and denture stability with combined or exclusive root support (P < .05 and .02, respectively). Initial costs of overdentures with combined or root support were 10% lower than for implant overdentures. CONCLUSION: The concept of combined root and implant support can be integrated into treatment planning and overdenture design for patients with a highly reduced dentition.

Comparisons of bacterial patterns present at implant and tooth sites in subjects on supportive periodontal therapy. I. Impact of clinical variables, gender and smoking

OBJECTIVE: (I) To compare the oral microflora at implant and tooth sites in subjects participating in a periodontal recall program, (II) to test whether the microflora at implant and tooth sites differ as an effect of gingival bleeding (bleeding on probing (BOP)), or pocket probing depth (PPD), and (III) to test whether smoking and gender had an impact on the microflora. MATERIAL AND METHODS: Data were collected from 127 implants and all teeth in 56 subjects. Microbiological data were identified by the DNA-DNA checkerboard hybridization. RESULTS: PPD> or =4 mm were found in 16.9% of tooth, and at 26.6% of implant sites (P<0.01). Tooth sites with PPD> or =4 mm had a 3.1-fold higher bacterial load than implant sites (mean difference: 66%, 95% confidence interval (CI): 40.7-91.3, P<0.001). No differences were found for the red, orange, green, and yellow complexes. A higher total bacterial load was found at implant sites with PPD> or =4 mm (mean difference 35.7 x 10(5), 95% CI: 5.2 (10(5)) to 66.1 (10(5)), P<0.02 with equal variance not assumed). At implant sites, BOP had no impact on bacterial load but influenced the load at tooth sites (P<0.01). CONCLUSION: BOP, and smoking had no impact on bacteria at implant sites but influenced the bacterial load at tooth sites. Tooth sites harbored more bacteria than implant sites with comparable PPD. The 4 mm PPD cutoff level influenced the distribution and amounts of bacterial loads. The subject factor is explanatory to bacterial load at both tooth and implant sites.

Comparison of bacterial plaque samples from titanium implant and tooth surfaces by different methods

Studies have shown similarities in the microflora between titanium implants or tooth sites when samples are taken by gingival crevicular fluid (GCF) sampling methods. The purpose of the present study was to study the microflora from curette and GCF samples using the checkerboard DNA-DNA hybridization method to assess the microflora of patients who had at least one oral osseo-integrated implant and who were otherwise dentate. Plaque samples were taken from tooth/implant surfaces and from sulcular gingival surfaces with curettes, and from gingival fluid using filter papers. A total of 28 subjects (11 females) were enrolled in the study. The mean age of the subjects was 64.1 years (SD+/-4.7). On average, the implants studied had been in function for 3.7 years (SD+/-2.9). The proportion of Streptococcus oralis (P<0.02) and Fusobacterium periodonticum (P<0.02) was significantly higher at tooth sites (curette samples). The GCF samples yielded higher proportions for 28/40 species studies (P-values varying between 0.05 and 0.001). The proportions of Tannerella forsythia (T. forsythensis), and Treponema denticola were both higher in GCF samples (P<0.02 and P<0.05, respectively) than in curette samples (implant sites). The microbial composition in gingival fluid from samples taken at implant sites differed partly from that of curette samples taken from implant surfaces or from sulcular soft tissues, providing higher counts for most bacteria studied at implant surfaces, but with the exception of Porphyromonas gingivalis. A combination of GCF and curette sampling methods might be the most representative sample method.

Influence of the condition of the adjacent tooth surface on fluorescence measurements for the detection of approximal caries

The aim of this study was to test whether the status of the adjacent tooth surface has an influence on the signal of a new laser fluorescence (LF) device for the detection of approximal caries. Seventy-eight teeth were selected from a pool of extracted permanent human molars, frozen at -20 degrees C until use. Before being measured the teeth were defrosted, cleaned, and any calculus removed. As a control, a defined approximal surface of each tooth was measured with the LF device holding the tip with the detecting- and the reverse-side on it, but without a neighboring tooth contacting the surface. The proximal site under examination was then placed adjacent to a tooth, which had deep dentinal caries, a composite restoration, a provisional ZnO-Eugenol restoration, or a ceramic restoration. The adjacent tooth with the ZnO-Eugenol restoration, the composite restoration, and the dentinal caries all demonstrated a statistically significant increase of LF readings on sound tooth surfaces. Teeth with enamel or dentinal caries were only slightly (and not statistically significantly) influenced by the different types of neighboring surfaces compared with the control LF readings. It can be concluded that caries detection of approximal tooth surfaces with the new LF system might be influenced by the condition of the adjacent tooth surface.

Erosive tooth wear: diagnosis, risk factors and prevention

PURPOSE: To provide an overview on diagnosis, risk factors and prevention of erosive tooth wear, which is becoming an increasingly important factor when considering the long- term health of the dentition. RESULTS: Awareness of dental erosion by the public is still not widespread due to the cryptic nature of this slowly progressing condition. Smooth silky-glazed appearance with the absence of perikymata and intact enamel along the gingival margin, with cupping and grooving on occlusal surfaces are some typical signs of enamel erosion. In later stages, it is sometimes difficult to distinguish between the influences of erosion, attrition or abrasion during a clinical examination. Biological, behavioral and chemical factors all come into play, which over time, may either wear away the tooth surface, or potentially protect it. In order to assess the risk factors, patient should record their dietary intake for a distinct period of time. Based on these analyses, an individually tailored preventive program may be suggested to patients. It may comprise dietary advice, optimization of fluoride regimes, stimulation of salivary flow rate, use of buffering medicaments and particular motivation for non-destructive tooth brushing habits. The frequent use of fluoride gel and fluoride mouthrinse in addition to fluoride toothpaste offers the opportunity to minimize abrasion of tooth substance.

Risk factors for reperfusion injury after lung transplantation

OBJECTIVE: To assess the influence of recipient's and donor's factors as well as surgical events on the occurrence of reperfusion injury after lung transplantation. DESIGN AND SETTING: Retrospective study in the surgical intensive care unit (ICU) of a university hospital. METHODS: We collected data on 60 lung transplantation donor/recipient pairs from June 1993 to May 2001, and compared the demographic, peri- and postoperative variables of patients who experienced reperfusion injury (35%) and those who did not. RESULTS: The occurrence of high systolic pulmonary pressure immediately after transplantation and/or its persistence during the first 48[Symbol: see text]h after surgery was associated with reperfusion injury, independently of preoperative values. Reperfusion injury was associated with difficult hemostasis during transplantation (p[Symbol: see text]=[Symbol: see text]0.03). Patients with reperfusion injury were more likely to require the administration of catecholamine during the first 48[Symbol: see text]h after surgery (p[Symbol: see text]=[Symbol: see text]0.014). The extubation was delayed (p[Symbol: see text]=[Symbol: see text]0.03) and the relative odds of ICU mortality were significantly greater (OR 4.8, 95% CI: 1.06, 21.8) in patients with reperfusion injury. Our analysis confirmed that preexisting pulmonary hypertension increased the incidence of reperfusion injury (p[Symbol: see text]<[Symbol: see text]0.01). CONCLUSIONS: Difficulties in perioperative hemostasis were associated with reperfusion injury. Occurrence of reperfusion injury was associated with postoperative systolic pulmonary hypertension, longer mechanical ventilation and higher mortality. Whether early recognition and treatment of pulmonary hypertension during transplantation can prevent the occurrence of reperfusion injury needs to be investigated.

Liver transplantation for patients with metastatic endocrine tumors: single-center experience with 15 patients

In contrast to other secondary liver malignancy, orthotopic liver transplantation (OLT) is considered as a treatment modality for nonresectable endocrine liver metastases in selected patients. However, only few series have assessed patient selection criteria and long-term results, and no reports have focused on the impact of new technologies in this regard. Between 1992 and 2004, 28 patients with malignant endocrine tumors underwent evaluation for OLT according to our protocol. Data were entered into a prospective database. During pretransplant evaluation, somatostatin receptor scintigraphy detected extrahepatic metastases not diagnosed in standard imaging in 10 patients. Of them, 3 showed aberrant Ki67 labeling results. One patient was excluded from further evaluation due to severe carcinoid heart. Thus far, 15 patients, 10 men and 5 women, aged 37 to 67 years, were subjected to the transplant procedure (11 deceased donor OLT, 3 living donor liver transplantations, and 1 cluster transplantation). Four patients died during the hospital treatment. The median follow-up of the discharged patients was 60.8 months. The actuarial patient survival was 78.3% at 1 year and 67.2% at 5 years. The actuarial 1-, 2-, and 5-year tumor-free survival amounted to 69.4%, 48.3%, and 48.3%, respectively. Two patients underwent surgery for isolated tumor recurrence. In 2 patients, peptide receptor radiotherapy was carried out because of multilocular recurrent disease. In conclusion, liver transplantation is a realistic therapeutic option for highly selected patients with hepatic metastases of endocrine tumors. Our strategy, which implements strict pretransplant selection and aggressive surgical approach, in case of disease recurrence, in addition to systemic radiopeptide treatment, led to an excellent long-term survival cure, however, is unlikely to be achieved.