The Effect of Sirolimus Therapy on Vaccine Responses in Transplant Recipients

Different immunosuppressant regimens vary in their effects on antibody responses to vaccination. The combination of prednisolone and azathioprine has only a minor effect, whereas the addition of ciclosporin attenuates protective antibody responses to influenza vaccination. The effect of sirolimus, a new immunosuppressant, on vaccine responses has been little studied. Thirty-two hepatic or renal transplant patients randomized to calcineurin inhibitor-based or sirolimus-based immunosuppression were vaccinated against influenza and pneumococcus. Following tri-valent influenza vaccination, a similar rise in antibody titer occurred in sirolimus and calcineurin inhibitor (CNI) treated patients, though sirolimus treated patients developed a 'protective' titer to more influenza antigens. The pneumococcal polysaccharide vaccine was equally effective in both groups. Hence, vaccination guidelines in place for CNI treated patients are likely to be appropriate for transplant recipients maintained on sirolimus.     

Allopeptide-Specific CD4+ T Cells Facilitate the Differentiation of Directly Alloreactive Graft-Infiltrating CD8+ T Cells

To investigate the mechanism of CD4(+) T-cell help during the activation and differentiation of directly alloreactive CD8(+) T cells, we examined the development of obliterative airways disease (OAD) following transplantation of airways into fully mismatched recipient mice deficient in CD4(+) T cells. BALB/c trachea allografts became fibrosed significantly less frequently in B6 CD4(-/-) recipients as compared to wildtype controls. Furthermore, class I-directed cytotoxicity failed to develop in the absence of CD4(+) T cells. The infiltration of graft tissue by primed L(d)-specific directly alloreactive 2C CD8(+) T cells was not found to depend on the presence of CD4(+) T cells. Nevertheless, graft-infiltrating 2C CD8(+) T cells failed to express CD69 and granzyme B when CD4(+) T-cell help was unavailable. Importantly, reconstitution of B6 CD4(-/-) recipient mice with graft peptide-specific TCR-Tg CD4(+) T cells (OT-II or TEa) capable of recognizing antigen only on recipient APC allowed for full expression of CD69 and granzyme B by the directly alloreactive CD8(+) T cells and restored the capacity of recipients to reject their allografts. These results demonstrate that indirectly alloreactive CD4(+) T cells ensure the optimal activation and differentiation of graft-infiltrating directly alloreactive CD8(+) T cells independent of donor APC recognition.     

Lung Transplant Metalloproteinase Levels Are Elevated Prior to Bronchiolitis Obliterans Syndrome

Parenchymal disease in the allograft lung is associated with interstitial remodeling believed to be mediated by matrix metalloproteinases (MMPs). Recent studies suggest high levels of MMP-9 are associated with bronchiolitis obliterans syndrome (BOS) in lung transplant recipients. Since BOS occurs late in the posttransplant period and may be preceded by episodes of acute rejection or infection, which are associated with interstitial remodeling, we examined MMP profiles in allograft bronchoalveolar lavage (BAL) fluid in the early posttransplant period (preceding BOS). Gelatin zymography, protein array analysis and specific ELISA on BAL fluids from transplanted lungs indicated that MMP-8, MMP-9 and TIMP-1 were strongly expressed in allograft BAL fluid from stable patients, or those with infection or rejection compared to BAL fluid from normal volunteers. Elevated expression of MMP-8, MMP-9 and TIMP-1 occurred early, and was sustained for the 3.2 years covered in this study. Elevations of MMP-8, MMP-9 and TIMP-1 in the first 2 years posttransplant appear to be associated with lung transplantation itself, and not infection or rejection. These data suggest that ongoing and clinically silent MMP activity could perpetuate progressive disease in the allograft lung.     

PR01“A PICTURE SPEAKS A THOUSAND WORDS”– THE USE OF DIGITAL PHOTOGRAPHY AND THE INTERNET IN MONITORING FREE TISSUE TRANSFER

Purpose Post operative monitoring is crucial for the success of microsurgical free tissue transfer. Sophisticated and expensive methods are available for monitoring. We propose a novel technique using digital photography and the internet as a reliable and cost effective method to monitor free tissue transfers. Methods 163 micro‐vascular procedures were monitored using this technique over 8 months. Serial photographs taken to show flap color. Capillary refill time, pin prick‐ bleed time and color and hand held Doppler signal was recorded in the movie mode of a standard 5 mega pixel camera with duration of 15 seconds. Data was sent to the surgeon at regular intervals and or as deemed necessary. Results Analysis of the 67 cases is presented. 5 re‐explorations were done. The early diagnosis of venous congestion was possible using this technique. Timely intervention contributed to the success of the re‐explorations and these flaps could be salvaged. The file size of images was in the range of 1 MB–6 MB. The file size of an entire set of images ranged about 7 MB–9 MB. These were sent across the ADSL internet lines. Conclusion The use of the digital images and the internet allow reconstructive surgeons to have a reliable picture of the state of their free tissue transfers. This permits decrease in observer error and saves valuable time which otherwise needs to be spent to verify situations of doubt and offers an ideal solution to the logistic problem of having to visit the patient in case of doubt.     

General and specific cognitive deficits in schizophrenia.

BACKGROUND: It is controversial whether the cognitive deficit in schizophrenia is better characterized as generalized or as reflecting relatively independent deficits in different cognitive domains. The issue has implications for assessment practice, intervention design, and the exploration of schizophrenia genetics. METHODS: We used a specialized structural equation modeling approach, single common factor analysis, to explore the relative importance of generalized versus independent cognitive deficits in schizophrenia. Eighteen subtest scores from the Wechsler Adult Intelligence Scale-III and the Wechsler Memory Scale-III were included in the analysis. We analyzed these data for 97 schizophrenia or schizoaffective disorder outpatients and 87 healthy control subjects. RESULTS: Approximately two thirds of the overall effect of a schizophrenia diagnosis on cognitive performance was mediated through a single common factor. The Wechsler subtest scores showed almost uniformly strong relationships with this factor. The independent associations of group status with the subtest scores were smaller in magnitude and only selectively significant. CONCLUSIONS: The relatively greater magnitude of illness effects mediated through the common factor in this analysis, compared with the specific, independent effects, suggests that a generalized cognitive deficit is a core feature of schizophrenia.     

Unterkieferrekonstruktion mit autologem Knochen und einem induktiven Implantat beim G?ttinger Minischwein

ZusammenfassungFragestellung In der vorliegenden Studie am Göttinger Minischwein wurde die direkte Rekonstruktion des Unterkiefers nach ausgedehnter Kontinuitätsresektion mit autologem Knochen und einem osteoinduktiven Implantat untersucht.Methode An neun ausgewachsenen Göttinger Minischweinen wurde ein einseitiger, 5 cm langer Unterkieferkontinuitätsdefekt gesetzt. Die Rekonstruktion erfolgte bei vier Tieren mit einem 50×25×15 mm³ großen, kollagenen Träger, dotiert mit rhBMP-2 (400 µg/cm³). Bei zwei Tieren wurde nur der Träger alleine implantiert und bei drei Tieren das lokal resezierte Knochensegment replantiert. Die Knochenregeneration und Konsolidierung der Defekte wurde radiologisch und histologisch analysiert.Ergebnisse Nach Rekonstruktion mit dem osteoinduktiven Implantat zeigte sich bei allen Versuchstieren eine komplette knöcherne Konsolidierung des gesetzten Unterkieferkontinuitätsdefekts. Der gesamte Defekt wurde von einem biomechanisch hochwertigen, sich funktionell anpassenden Knochen überbrückt. Nach Replantation des ortsständigen autologen Knochens wird dieser nicht schnell genug knöchern integriert. In der Peripherie bilden sich nur unvollständige Knochenbrücken aus; dies führt zum vollständigen Versagen der Rekonstruktion. Ebenso findet bei der Implantation des Trägers alleine keine Konsolidierung statt.Schlussfolgerung Die direkte Rekonstruktion eines ausgedehnten, biomechanisch belasteten Defekts mit einem osteoinduktiven Implantat erwies sich als die überlegene Methode. Das hierbei entstehende knöcherne Regenerat erfährt eine unmittelbare funktionelle Strukturierung. Die Notwendigkeit zu extensiven adaptiven Umbauvorgängen wird hierdurch minimiert.     

Bioartifizielle Materialien in der Urologie

The scope of our research is the development of polymer-based bioabsorbable stents for urologic applications and in vitro testing of tissue reactions of cultured ureteral and urethral segments induced by implanted polymer stent prototypes. For these purposes a tissue cultivation model was developed using selected techniques of tissue engineering. Essential advantages of degradable over nondegradable urethral stents are elimination of the adverse extraction of epithelialized stents and the potential for recovery of organ-specific functionality. Moreover, the biocompatibility of a degradable urethral stent could potentially reduce the risk of restenosis due to hyperplasia and could be used, even repeatedly, for the treatment of a number of subvesical obstructions. For the treatment of tumor-induced strictures, application of degradable polymer stents coated with cytostatic drugs may be possible. The mechanical effect of the drug-loaded stent as a “place holder” could be complemented by adjuvant or palliative approaches such as local chemotherapy. We have developed and tested in vitro a degradable urethral stent incorporated with the model drug methotrexate for local drug delivery (LDD) by diffusion and during stent degradation.     

Impact of neuronavigation and image-guided extensive resection for adult patients with supratentorial malignant astrocytomas: a single-institution retrospective study.

Neuronavigation has become an effective therapeutic modality and is used routinely for intra-axial tumor removal. This retrospective study was conducted to evaluate the clinical impact of neuronavigation and image-guided extensive resection for adult patients with supratentorial malignant astrocytomas. Between 1990 and 2002, 76 adult patients with pathologically confirmed malignant astrocytomas underwent craniotomy and removal of the tumors at the Toyama Medical and Pharmaceutical University Hospital. Of these 76 patients, 42 were treated using neuronavigation with conventional microneurosurgery and the other 34 were treated with conventional microneurosurgery alone. Postoperative early MRI with contrast enhancement was done, and gross total resection was defined as the complete absence of residual tumor. Survival time was analyzed with the Kaplan-Meier method. Prognostic factors were obtained from the Cox proportional hazards model. In univariate analysis, age (< 65), grade 3, preoperative KPS (>/= 80), use of neuronavigation, and gross total resection were significantly associated with longer survival. However, when the data were submitted to multivariate analysis, grade 3, preoperative KPS (>/= 80), and gross total resection were independent prognostic factors. The median survival periods of patients receiving gross total resection (vs. partial resection) and neuronavigation (vs. no neuronavigation) were 16 (vs. 9) months and 16 (vs. 10) months, respectively. The percentage of a gross total resection was significantly higher in the neuronavigation group compared to that in the no-navigation group (64.3 % vs. 38.2 %, p < 0.05). Neurological deterioration occurred in 4 of 42 (9.5 %) and in 6 of 34 (17.6 %) patients after surgery with neuronavigation and surgery without neuronavigation, respectively, although this difference was not statistically significant. Our results showed that neuronavigation increases the radicality in the resection of malignant astrocytomas and is objectively useful for improving survival time.