Extended apical enlargement with hand files versus rotary NiTi files. Part II.

OBJECTIVE: The objective of this study was to compare 2 preparation techniques performed under simulated clinical conditions with extended apical enlargement following determination of the optimal apical preparation size (APS). STUDY DESIGN: After preflaring 240 root canals, APS was evaluated as outlined in Part I. The apical portion was shaped to APS either with rotary NiTi Lightspeed instruments (LS) or NiTi hand instruments (HA) using the balanced force technique in a phantom head. After sectioning the apical area at 3 levels, every cross section was analyzed microscopically for circumferential removal of canal wall dentine. Loss of working length, instrument separation, and perforation were additionally recorded. RESULTS: In 70% (LS) and 69% (HA) of the root canals, 2 of 3 levels demonstrated that the root canal dentin was cut circumferentially. Neither loss of working length nor perforation occurred in both groups. Four LS instruments separated. CONCLUSIONS: APS frequently results in a nearly complete apical preparation regardless of the preparation techniques. In a few cases apical enlargement to APS does not achieve complete cutting of the canal walls. There was a rather slight risk of serious procedural errors.     

Interleukin-4 as a potent down-regulator for human alveolar macrophages capable of producing tumour necrosis factor-alpha and interleukin-1.

The effects of recombinant human interleukin-4 (IL-4) on the production of interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF alpha) by human alveolar macrophages (AM) and autologous peripheral blood monocytes (PBM) in response to lipopolysaccharide (LPS) were examined. AM and PBM were obtained by bronchoalveolar lavage and centrifugal elutriation, respectively, from healthy donors. The production of IL-1 (alpha and beta) and TNF alpha by human AM and PBM were quantitated by enzyme immunoassays (EIA). When activated with LPS, AM secreted much more TNF alpha, but less IL-1 beta than PBM. The production of IL-1 (alpha and beta) by activated AM and autologous PBM was suppressed dose-dependently by IL-4. The inhibitory effect of IL-4 was greatest when it was added to AM or PBM simultaneously with LPS or within 3 h after LPS. The suppressive effect of IL-4 was completely neutralized by pretreatment with rabbit anti-IL-4 antiserum. IL-4 also suppressed the production of IL-1 and TNF alpha by monocyte-derived macrophages. As measured by thymocyte co-stimulation assay, the production of cell-associated IL-1 was inhibited by coculture of AM plus LPS with IL-4. Northern blot analysis showed suppression by IL-4 of expression of messenger ribonucleic acid (mRNA) for IL-1 and TNF alpha in LPS-stimulated AM. We conclude that IL-4 is a potent down-regulator for human alveolar macrophages capable of producing IL-1 and TNF alpha.     

Analysis of three-dimensional sinter shrinkage of copings made from alumina in an innovative direct shaping process.

The three-dimensional (3D) evaluation and comparison of free-form-surfaces is a complex problem [Dent. Mater. 8 (1992) 49; J. Dent. Res. 76 (1997) 1799; Dent. Mater. 16 (2000) 145; J. Prosthet. Dent. 70 (1993) 457; Dent. Mater. 19 (2003) 19]. However, it is essential in order to analyze the sinter shrinkage of dental ceramic-restorations where isotropic and linear shrinkage is desired for accurate fit on the prepared teeth. In this article, we examine the 3D sinter shrinkage in general and for nine copings from alumina in particular. Using various scaled CAD-models in an iteration scheme, each model was compared to the filtered point cloud of the coping, determining the surface-cloud difference. The magnitude of deviations from linear sinter shrinkage was investigated. Furthermore, a new fabrication process for ceramic-restorations is introduced.     

Human Herpesvirus 6 in Bronchalveolar Lavage Fluid after Lung Transplantation: A Risk Factor for Bronchiolitis Obliterans Syndrome?

Bronchiolitis obliterans syndrome (BOS) is the limiting factor to long-term survival after lung transplantation. Previous studies suggested respiratory viral tract infections are associated with the development of BOS. To identify the impact of virus detection in bronchoalveolar lavage (BAL) fluid, we analyzed BAL samples from 87 consecutive lung transplant recipients for human herpesvirus (HHV)-6, Epstein-Barr virus, Herpes simplex virus 1/2, Cytomegalovirus, respiratory syncytical virus and adenovirus by PCR. Acute rejection, BOS and death were recorded for a mean follow-up time of 3.27 +/- 0.47 years. Results of PCR analysis and other potential risk factors were entered into a Cox regression analysis of BOS predictors and death. Only acute rejection was a distinct risk factor for BOS of all stages, death and death from BOS. HHV-6 was detected in 20 patients. Univariate and multivariate analysis revealed that HHV-6 was associated with an increased risk to develop BOS > orb = stage 1 and death, separate from the risk attributable to acute rejection. Identification of HHV-6 DNA in BAL fluid is a potential risk factor for BOS. Our results warrant further studies to elucidate a possible causal link between HHV-6 and BOS.     

Ventricular enlargement, clinical correlates and treatment outcome in chronic schizophrenic inpatients.

The ventricle-brain ratio (VBR) of 42 chronic schizophrenic patients was compared with that of 42 age-matched medical controls. For the schizophrenics, the relationship of various clinical parameters to the VBR was assessed, and the outcome of 12 weeks of double-blind treatment with either risperidone or haloperidol. The results confirm that schizophrenic patients have slightly enlarged lateral ventricles compared with medical controls. Only for schizophrenics, an effect of age, but not of duration of illness, was noticed. This study does not support the validity of a clinical subdivision of chronic schizophrenic patients on the basis of the VBR. Neither negative, positive nor general psychopathological symptoms, as measured by the Positive and Negative Syndrome Scale for Schizophrenia (PANSS), were related to the VBR, nor were abnormal involuntary movements or extrapyramidal symptoms. No association between season of birth or a family history of major mental disorder and VBR could be demonstrated. Treatment response was predicted by the total PANSS score and the PANSS general psychopathology subscale score at baseline. There was a trend for patients with higher VBR to have a more or haloperidol). or haloperidol).     

Stereotactic brain biopsy in AIDS

Summary In the hope of finding a treatable condition, the need for rapid diagnosis in HIV-seropositive patients with brain lesions is apparent. In order to evaluate the efficacy of stereotactic brain biopsy in AIDS patients, we retrospectively studied 25 HIV-infected patients undergoing stereotactic biopsy. Brain lesions were identified with gadolinium-enhanced MRI and/or contrastCT. Brain biopsy was performed using the system of Riechert. From 8 up to 15 small tissue samples from one or two targets were obtained in every patient. The biopsy material was examined cytologically, histologically (including electron microscopy), immunohistochemically and, in part, by animal test and polymerase chain reaction (PCR). A definite diagnosis was achieved in 92%. Diagnosis included primary central nervous system lymphoma (PCNSL) (10), toxoplasmosis (10), progressive multifocal leukoencephalopathy (2) and one case of co-existing toxoplasmosis and cytomegalovirus infection. Two biopsies were non-diagnostic. All PCNSLs showed polymorphic B-cell populations of high malignancy; accurate classification according to the Kiel classification was not possible. In 3 lymphomas Epstein-Barr nuclear antigen (EBNA) 2-mRNA could be detected by PCR and confirmed immunohistochemically by EBNA 2 expression. In 6 cases autopsy confirmed the biopsy diagnosis. Conventional histology was not sufficiently decisive for toxoplasmosis and progressive multifocal leukoencephalopathy, so that immunohistochemistry and animal tests became very important for a final diagnosis. With the help of different morphological and molecular biological techniques stereotactic brain biopsy appears to be an effective method in the diagnosis of HIV-associated brain lesions. In view of the marked radio- and chemosensitivity of PCNSLs it is mandatory to establish an early and accurate histological diagnosis for adequate treatment.     

Primary porcine proximal tubular cells as a model for transepithelial drug transport in human kidney.

BACKGROUND: Kidney proximal tubular cells play a major role in the transport of endogenous and exogenous compounds. A multitude of different transporters are expressed starting with multidrug ABC transporters (e.g. abcb1, abcc1-6), slc22a6-8 (organic anion transporters) and slc22a1-3 (organic cation transporters). For transport studies of renal drug transport, cell lines like MDCK and LLC-PK1 are often used to overexpress and study one or two transporters, such as abcb1 or abcc1-6. However, the use is limited since under physiological conditions xenobiotics are transported through different transporters at the same time. Therefore, a primary in vitro model expressing functionally different transporters simultaneously, as it is the case in vivo, would be of great benefit. METHODS: Primary proximal tubular cells were isolated from porcine kidney. Cells were cultured under selective culturing conditions leading to specific growth of primary proximal tubular cells. Expression of important proximal transporters was checked at mRNA level with RT-PCR, at protein level with immunocytochemistry and functionally by transport and uptake assays. RESULTS: A model of primary proximal tubular cells was established expressing the most important transporters: abcb1, abcc1, abcc2, slc22a8, slco1a2, slc15a1, slc5a2 and slc4a4. In freshly isolated cells, slc22a1 and slc22a6 were expressed, but were down-regulated in culture. Abcb1, abcc1, abcc2 and slc4a4 were detected at protein level with immunostaining. Functional activity was confirmed for abcb1, abcc1/2, slc22a8, slc15a1/2 and slc5a1/2. The tightness of the monolayers of this model was better than in previously established in vitro models. CONCLUSION: This primary cell culture model might be an interesting tool to investigate proximal tubular transport and to predict toxicity and drug interactions since it expresses functionally several transporters simultaneously.     

MR Lymphography with a Lymphotropic T1-Type MR Contrast Agent: Gd-DTPA-PGM

A model system of a paramagnetic lymphotropic MR contrast agent (Gd-DTPA labeled polyglucose associated macrocomplex, PGM) for T¹-weighted MR imaging of lymph nodes in rats and rabbits was evaluated. Pharmacokinetic (tissue accumulation) and MR imaging data (optimal dose and timing parameters) were obtained in normal rats (n = 88) after subcutaneous (SC) injection of paramagnetic, radiolabeled [111In]Gd-DTPA-PGM. A rabbit model of lymph node metastases (n = 8) was ultimately used to demonstrate the potential of MR imaging with Gd-DTPA-PGM for nodal tumor detection. Maximum concentrations of Gd-DTPA-PGM were found in popliteal and paraaortic lymph nodes within 24 h after SC administration, and highest lymph node SNR values were obtained by MR imaging at this time point. The optimum imaging dose was 6–12 μmol Gd/kg. Tumor-lymph node contrast increased from 0.0 ± 1.2 precontrast to 19.2 ± 6.5 (spoiled gradient echo sequence, TR 50/TE 7/flip angle 60°) postcontrast and conspicuity of nodal metastases was improved. Gd-DTPA-PGM accumulates in lymph nodes after SC administration and significantly enhances lymph node signal intensity of normal animals but not metastatic lymph nodes.