Tip Design of Hemodialysis Catheters Influences Thrombotic Events and Replacement Rate.

OBJECTIVE/BACKGROUND: Central venous tunnelled hemodialysis catheters (CVTC) are used for initial vascular access in patients with renal failure. Tip design of the CVTC may play an important role in catheter function and complication rates, influencing adequate hemodialysis treatment of these patients. METHODS: This prospective, observational cohort study compared the function and complication rates of two CVTCs in patients with end stage renal disease (ESRD) within a follow-up period of 24 months. The study included patients with ESRD who received either a CVTC with a split tip (ST) or a shotgun tip (SG). All patients underwent dialysis within 24 h of intervention. Blood flow was documented initially (Qb0) and was followed up after 6 (Qb6), 12 (Qb12), and 24 (Qb24) months. Analysis of blood flow and complication rates within the follow-up period was performed by questionnaires. RESULTS: In total, 185 patients were included, of whom 93 received a ST CVTC and 92 a SG CVTC. Baseline parameters did not differ significantly between groups. CVTC blood flow was not significantly different between the two devices. Thrombolytic therapy with Alteplase was used significantly more often in the ST group (29%) than in the SG group (16%) (p < 0.05). The CVTC replacement rate was significantly higher in the ST group (19.3%) compared with the SG group (8.7%) (p < 0.05). CONCLUSIONS: The tip design of CVTC (split or shotgun) appears to be irrelevant for long-term blood flow during dialysis treatment. However, patients may benefit from SG catheters over ST catheters where replacement rates and thrombolytic treatment are concerned.

Disruption of Staphylococcus aureus biofilms using rhamnolipid biosurfactants.

Staphylococcus aureus is an important pathogen that has shown ability to establish biofilm communities that can represent a source of contamination and resistance in food processing. Rhamnolipids (RL) have attracted attention as candidates to replace synthetic surfactants, exhibiting high surface activity combined with its microbial origin, biodegradability, and low toxicity. In this work, an RL biosurfactant was evaluated regarding its ability to disrupt or remove S. aureus biofilms established on polystyrene plates using nutrient broth and skim milk as the growth media. Rhamnolipid treatment was performed at different surfactant concentrations and temperatures. Rhamnolipid removes up to 88.9% of milk-based biofilms, whereas for nutrient medium 35% removal was attained. The RL concentration affects the disruption of nutrient medium-based biofilms. High carbohydrate content of milk-based biofilms favors disruption by RL and the organization of RL molecules in solution showed a predominance of aggregates from 1 to 10 and 100 to 1,000 nm in all conditions studied. Biofilm disruption activity of RL is nutrient-specific and dependent on biofilm matrix composition. Staphylococcus aureus biofilms established in milk were significantly reduced using RL at low concentrations and temperatures. These findings suggest potential application of RL in milk (dairy) processing industries where low temperatures are applied.

An 8-week injury prevention exercise program combined with change-of-direction technique training limits movement patterns associated with anterior cruciate ligament injury risk.

Knee ligament sprains are common during change-of-direction (COD) maneuvers in multidirectional team sports. This study aimed to compare the effects of an 8-week injury prevention exercise program containing COD-specific exercises and a similar program containing linear sprint exercises on injury- and performance-related variables during a 135° COD task. We hypothesized that the COD-specific training would lead to (H1) stronger reductions in biomechanical variables associated with anterior cruciate ligament (ACL) injury risk during COD, i.e. knee abduction moment and angle, hip internal rotation angle and lateral trunk lean, and (H2) more effective improvements in COD performance according to the COD completion time, executed angle, ground contact time, and approach speed. Twenty-two sports science students (40% female) completed biomechanical assessments of COD movement strategies before and after participating in two supervised 25-min training sessions per week over 8 weeks. We observed significant 'training x group' interaction effects in support of H1: the COD-specific training but not the linear sprint training led to reduced peak knee abduction moments (interaction, p = 0.027), initial knee abduction (interaction, p < 0.001), and initial lateral trunk lean angles (interaction, p < 0.001) compared to baseline. Although the COD-specific training resulted in sharper executed angles (interaction, p < 0.001), the sprint-specific training group showed reduced COD completion (interaction, p = 0.037) and ground contact times (interaction, p < 0.001). In conclusion, a combination of generic and COD-specific injury prevention training resulted in COD technique adaptations that can help to avoid ACL injury-prone COD movements but may negatively affect COD speed.

[Transplantation of corneal endothelium--chances and challenges]. / Die Transplantation des kornealen Endothels--Möglichkeiten und Grenzen.

BACKGROUND: Endothelial keratoplasty is a promising surgical procedure which may replace penetrating keratoplasty in cases of endothelial cell diseases of the cornea. This method may thereby help to prevent postoperative astigmatism and transplant rejection. METHODS AND RESULTS: A survey of publications reporting about results after endothelial keratoplasty shows that the main problem of this transplantation technique is a postoperative endothelial cell loss which is comparable to or even higher than that observed in penetrating keratoplasty. Improving surgical techniques led to a reduction of the endothelial cell loss, however, cell-based strategies to prevent postoperative cell loss or to enhance the cell densities of donor corneas or endothelial lamellae are rare. DISCUSSION: This review presents an overview of clinical results after endothelial keratoplasty. Current strategies in the field of cell biology and tissue cultivation of corneal endothelial cells, genetic manipulation of the corneal endothelium and tissue engineering strategies aiming at the production of transplantable endothelial cell sheets are described. CONCLUSION: The limited availability of donor corneas makes it mandatory to develop methods in the field of tissue engineering in order to improve corneal endothelial cell survival or to increase corneal endothelial cell density, using interdisciplinary approaches.

Surfactin reduces the adhesion of food-borne pathogenic bacteria to solid surfaces.

AIMS: To investigate the effect of the biosurfactants surfactin and rhamnolipids on the adhesion of the food pathogens Listeria monocytogenes, Enterobacter sakazakii and Salmonella Enteritidis to stainless steel and polypropylene surfaces. METHODS AND RESULTS: Quantification of bacterial adhesion was performed using the crystal violet staining technique. Preconditioning of surfaces with surfactin caused a reduction on the number of adhered cells of Ent. sakazakii and L. monocytogenes on stainless steel. The most significant result was obtained with L. monocytogenes where number of adhered cells was reduced by 10(2) CFU cm(-2). On polypropylene, surfactin showed a significant decrease on the adhesion of all strains. The adsorption of surfactin on polystyrene also reduces the adhesion of L. monocytogenes and Salm. Enteritidis growing cells. For short contact periods using nongrowing cells or longer contact periods with growing cells, surfactin was able to delay bacterial adhesion. CONCLUSIONS: The prior adsorption of surfactin to solid surfaces contributes on reducing colonization of the pathogenic bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first work investigating the effect of surfactin on the adhesion of the food pathogens L. monocytogenes, Ent. sakazakii and Salm. Enteritidis to polypropylene and stainless steel surfaces.

Morphological basis for the spectrum of clinical deficits in spinocerebellar ataxia 17 (SCA17).

Spinocerebellar ataxia 17 (SCA17) is a rare genetic disorder characterized by cerebellar, extrapyramidal, pyramidal as well as psychiatric signs. The pathoanatomical basis of this disorder is still not well known. A total of 12 patients and 12 age- and sex-matched controls were examined by in vivo MRI voxel-based morphometry (VBM). Besides general patterns of disease-related brain atrophy, characteristic syndrome-related morphological changes in SCA17 patients were studied. In comparison with normal controls, SCA17 patients showed a pattern of degeneration of the grey matter centred around mesial cerebellar structures, occipito-parietal structures, the anterior putamen bilaterally, the thalamus and other parts of the motor network, reflecting the cerebellar, pyramidal and extrapyramidal signs. A correlation analysis revealed a clear association between the clinical cerebellar, extrapyramidal and psychiatric scores and degeneration in specific areas. Two degeneration patterns were found as follows: regarding motor dysfunction, atrophy of the grey matter involved mainly the cerebellum and other motor networks, in particular the basal ganglia. In contrast, correlations with psychiatric scores revealed grey matter degeneration patterns in the frontal and temporal lobe, the cuneus and cingulum. Most interestingly, there was a highly significant correlation between the clinical Mini-Mental State Examination scores and atrophy of the nucleus accumbens, probably accounting for the leading psychiatric signs.

Structural and Functional Adaptation of the Remnant Kidney After Living Kidney Donation: Long-Term Follow-up.

OBJECTIVE: Several adjustments occur after nephrectomy (NT) in the donor's remnant kidney. We investigated kidney donors 10 years after NT and compared several parameters before and after transplantation. METHODS: A total of 42 kidney donors of the University of Luebeck's Transplant Center were scheduled for a 10-year follow-up and were offered several investigations: laboratory tests, urinalysis and kidney ultrasound examination including determination of kidney volume (KV), resistive index (RI) and pulsatility index (PI). Moreover, a 24-hour ambulatory blood pressure monitoring (ABPM) was performed. A review of the medical records allowed comparison of the investigated parameters before (t0), 1 month after (t0.1), and 10 (t10) years after NT. RESULTS: Creatinine clearance decreased from 94.3 ± 23 (t0) to 52.4 ± 22 mL/min/1.73 m2 (t0.1) and increased to 78.2 ± 19 mL/min/1.73 m2 after 10 years (t10). Tubular proteinuria (α1-microglobuline) increased from 6.1 ± 1.5 (t0) to 63 ± 4.8 (t0.1) (P < .05) and decreased to 36 ± 2.4 mg/g creatinine at t10 (P < .05). Ultrasound examinations revealed a growth of the KV from 159.8 ± 23.1 (t0) to 175.5 ± 22.1 mL (t10) (P < .05) and an increase of RI and PI from t0 of 0.63 ± 0.01 and 1.03 ± 0.03 to t10 of 0.72 ± 0.04 (P < .05) and 1.24 ± 0.11 (P < .05), respectively. Post-NT ABPM values were not significantly different from pre-NT values. CONCLUSIONS: NT leads to hypertrophy of the remnant kidney associated with an increase of organ volume and creatinine clearance after 10 years of follow-up. Our results indicate an excellent prognosis for the kidney donors without any signs of renal damage.

The cerebellum in the cerebro-cerebellar network for the control of eye and hand movements--an fMRI study.

The coordination of optical information and manipulation of objects in space by eye and hand movements is controlled by a cerebro-cerebellar network. The differential influence of prefrontal, motor, or parietal areas in combination with cerebellar areas, especially within the posterior hemispheres, on the control of eye and hand movements is not very well defined. Using fMRI we investigated the functional representation of isolated or combined eye and hand movements within the cerebellum and the impact of differential cognitive preload on the activation patterns. Each task consisted of the performance of saccades or hand movements triggered by a cue presented on a screen in front of the scanner. Saccades were tested for visually guided saccades, triple step saccades, and for visuospatial memory. Sequential finger opposition movements were tested for predictive and nonpredictive movements. Combined and isolated eye-hand reaching movements were tested toward a target presented in 5 different horizontal positions. Visually guided saccades activated the cerebellar vermis lobuli VI-VII, triple step saccades, including visuospatial memorization, in addition the cerebellar hemispheres lobuli VII-VIII. Sequential finger movements and reaching movements activated a cerebellar network consisting of the lobuli IV-VI, the vermis, and the lobuli VII-VIII with broader areas and additional regions especially within the lobus VII for more complex movements. The combined in contrast to the isolated performance of eye and hand movements demonstrated specialized activation foci within the cerebellar vermis and posterior hemispheres. We could demonstrate a differential representation of eye and hand movements within the cerebellum. Additional "cognitive" preload within a given task leads to additional activation of the posterior cerebellar hemispheres, with a subspecialization corresponding to premotor and parietal area connections.

Ethylene glycol intoxication and xylitol infusion--metabolic steps of oxalate-induced acute renal failure.

Acute renal failure is a major complication in patients with increased oxalate serum concentration. To describe the metabolic mechanisms of oxalate-induced glomerular and tubular damage, we report a case of ethylene glycol intoxication as well as a case of xylitol infusion in a patient with previously unknown primary hyperoxaluria type 1. Both patients presented with acute renal failure associated with histologically proven renal oxalate accumulation. This excessive oxalate overloading resulted from elimination and metabolization of ethylene glycol or xylitol. Thus, key enzymes in the elimination pathway of these substances represent targets for pharmacological treatment. Simultaneous hemodialysis is often necessary to reduce oxalate serum concentration. Whereas renal function of the ethylene glycol-poisoned patient recovered, the second patient who received xylitol infusion required chronic hemodialysis due to the unmasked hyperoxaluria type 1. Our cases demonstrate that patients with excessive endogenous oxalate generation are at high risk to develop acute renal failure. Therefore, to prevent end-stage renal failure in these patients, important clinical factors should be considered as indicators for the underlying cause: history of alcohol abuse and severe high anion gap acidosis for ethylene glycol intoxication or history of long-lasting parenteral nutrition for xylitol-associated acute renal failure.

Experimental studies of contact angle hysteresis phenomena on polymer surfaces ­ Toward the understanding and control of wettability for different applications.

Contact angle hysteresis phenomena on polymer surfaces have been studied by contact angle measurements using sessile liquid droplets and captive air bubbles in conjunction with a drop shape method known as Axisymmetric Drop Shape Analysis - Profile (ADSA-P). In addition, commercially available sessile drop goniometer techniques were used. The polymer surfaces were characterized with respect to their surface structure (morphology, roughness, swelling) and surface chemistry (elemental surface composition, acid-base characteristics) by scanning electron microscopy (SEM), scanning force microscopy (SFM), ellipsometry, X-ray photoelectron spectroscopy (XPS) and streaming potential measurements. Heterogeneous polymer surfaces with controlled roughness and chemical composition were prepared by different routes using plasma etching and subsequent dip coating or grafting of polymer brushes, anodic oxidation of aluminium substrates coated with thin polymer films, deposition techniques to create regular patterned and rough fractal surfaces from core-shell particles, and block copolymers. To reveal the effects of swelling and reorientation at the solid/liquid interface contact angle hysteresis phenomena on polyimide surfaces, cellulose membranes, and thermo-responsive hydrogels have been studied. The effect of different solutes in the liquid (electrolytes, surfactants) and their impact on contact angle hysteresis were characterized for solid polymers without and with ionizable functional surface groups in aqueous electrolyte solutions of different ion concentrations and pH and for photoresist surfaces in cationic aqueous surfactant solutions. The work is an attempt toward the understanding of contact angle hysteresis phenomena on polymer surfaces aimed at the control of wettability for different applications.

Double-blind crossover study with physostigmine in patients with degenerative cerebellar diseases.

OBJECTIVE: To determine whether treatment with physostigmine can improve the conditions of patients with ataxia. DESIGN: A double-blind crossover study with physostigmine was performed in 19 patients with degenerative cerebellar diseases. SETTING: Patients were selected from an ongoing prospective follow-up study at the university hospital in Lübeck, Germany. PATIENTS: Eleven patients with autosomal dominant cerebellar ataxia and 8 patients with idiopathic cerebellar ataxia. INTERVENTION: Physostigmine was administered by using a transdermal system (patch) containing 30 mg of physostigmine as a base, of which about 6 mg is released during 24 hours along a diffusion gradient. Each treatment phase with the physostigmine patch or the placebo lasted 4 weeks, after which the treatment of patients was crossed over to the other phase. MAIN OUTCOME MEASURES: Ataxia was documented and quantified by using a clinical score and posturographic measures. RESULTS: Physostigmine patches had no significant effect on cerebellar symptoms. CONCLUSION: Treatment with physostigmine does not improve the conditions of patients with ataxia.

Obliterative airway disease after heterotopic tracheal xenotransplantation: pathogenesis and prevention using new immunosuppressive agents.

BACKGROUND: The purpose of this study was to investigate whether obliterative bronchiolitis might occur after xenogenic pulmonary transplantation. A model for obliterative airway disease (OAD) after tracheal allograft transplantation in the rat undergoes tracheal obliteration with histologic features characteristic of obliterative bronchiolitis in human lung transplant recipients. Using this model, the pathogenesis of OAD and its prevention with immunosuppressive drugs was studied in rat recipients of hamster tracheal grafts. METHODS: Tracheae from 30 hamsters (xenografts) or 23 Brown-Norway rats (allografts) were implanted and wrapped in the greater omentum of untreated Lewis rats. The grafts were removed on day 1, 3, 7, 14, 21, or 28 after transplantation and stained with hematoxylin and eosin and Masson's trichrome and by immunohistochemistry and immunofluorescence (IFL) techniques. In addition, 25 recipients were treated with cyclosporine (CsA, 10 mg/kg p.o.), leflunomide (LFM, 20 mg/kg p.o.), or rapamycin (RPM, 6 mg/kg i.p.) for 14 or 21 days (5 animals per treatment group). Visual and morphometric analyses were used to evaluate the extent of airway obliteration, luminal coverage by respiratory or flattened cuboidal epithelium, and extent and density of peritracheal cellular inflammation. RESULTS: In all xenografts, a neutrophilic infiltration of the mucosa and submucosa was observed from day 1 until day 14 and was associated with complete loss of tracheal epithelium by day 14. A marked peritracheal mononuclear cellular infiltrate mixed with plasma cells and eosinophils was seen on days 7 and 14. Both the extent of peritracheal inflammation and the density of the mononuclear cell infiltrate were significantly increased in xenograft tracheae when compared with the allografts. Tracheal obliteration began on day 14 and reached a maximum of 43% on day 21 with evidence of intraluminal fibrosis. In contrast to IFL of allografts, IFL of xenografts demonstrated marked deposition of rat immunoglobulin in the peritracheal tissue on days 7 and 14. The effects of treatment with immunosuppressive drugs on tracheal graft narrowing and protection of respiratory epithelium were as follows: After 14 days of treatment, the percentage of tracheal graft narrowing was 12%, 23%, and 19% in the no treatment, CsA, and LFM groups, respectively; the percentage of respiratory epithelium at 14 days was 0%, 21%, and 95%. After 21 days of treatment, the percentage of tracheal graft narrowing was 43%, 49%, 12%, and 5% for the no treatment, CsA, LFM, and RPM groups, respectively; the percentage of respiratory epithelium at 21 days was 0%, 39%, 86%, and 0%. Using computerized morphometry, the extent and densities of the peritracheal cellular infiltrates were significantly reduced in LFM- and CsA-treated groups when compared with untreated xenograft controls. LFM and RPM, but not CsA, significantly reduced the degree of luminal obliteration compared with no treatment (P<0.05). LFM and, to a lesser extent, CsA were able to prevent the loss of normal respiratory epithelium. Analysis by IFL revealed a marked decrease in rat immunoglobulin deposition in xenografts from LFM- and RPM-treated groups compared with xenografts from CsA-treated or untreated rats. CONCLUSIONS: (1) OAD occurs not only after tracheal allotransplantation but also after xenotransplantation. (2) Subepithelial infiltration of neutrophils and the appearance of plasma cells and eosinophils in the peritracheal infiltrates distinguished the histology of rejected xenografts from allografts. (3) Antibody deposition was detected by IFL only in xenografts. (4) Treatment with LFM or RPM significantly decreased the severity of luminal obliteration. Importantly, LFM also prevented the loss of respiratory epithelium.

Cell-lines derived from human gliomas activate multiple autocrine pathways.

Fifteen permanent cell lines derived from maligant human gliomas and 5 sublines derived thereof were analyzed for the secretion of mitogenic activities. Conditioned media (c-med) from all cells were obtained from four to six day long periods of serum-free culture. The optimal conditioning time period resulting in maximal activity of the media varied between the cell lines. These conditioned media were added in final concentrations ranging from 5% to 60% to autologous and heterologous glioma cell cultures in serum-free conditions. These cultures were counted after 2, 4 and 6 days. It was observed, that there were two distinct groups of cells in respect to the response to the autologous media. 11 cell lines responded to their own c-med with dose dependent, enhanced rate of proliferation. The other cell lines proliferated in serum-free medium without response to the addition of c-med. Analyzing the responses to heterologous assays it was found, that media which did not show effect in the homologous system, were mitogenic for other cell lines. Also, cells which did not respond to their own media, responded to heterologous c-med. This study indicates, that in vitro two groups of glioma cell-lines can be distinguished in respect to the response pattern to autologous growth factors secretion. It was also seen, that the activities supporting proliferation did not act on five randomly chosen meningiomas in early culture, indicating some degree of lineage specificity. From this study it may be concluded that active growth factor secretion by tumor cells does not necessarily imply that the cells depend on such mechanism for maintenance of cell division, Furthermore, it needs to be acknowledged, that there may be a multiplicity of autocrine/paracrine growth factors secreted by individual cell lines and possibly tumors.

CD45 isoform expression in autoimmune myasthenia gravis.

In myasthenia gravis (MG), humoral and cellular immune mechanisms are involved in the autoimmune pathogenesis. In this study, we investigated the role of the CD45 molecule in MG, having recently reported an association in multiple sclerosis. CD45, a protein-tyrosine phophatase receptor type C (PTPRC), is essential for both thymic selection and peripheral activation of T and B cells. Our aims were to determine (a) the prevalence of a functional mutation in the CD45 gene (exon 4 77C --> G; prevalence analysis), and (b) the distribution of memory (CD45RO+) and naive (CD45RA+) T cells in the peripheral blood (subset analysis). T cells from 78 patients with generalised MG were stained with monoclonal antibodies against CD45RO, CD45RA, CD4 and CD8 and quantified by four-colour flow cytometry. The control panel for the prevalence analysis (a) consisted of 303 healthy individuals. (b) From those, 67 age- and sex-matched probands were randomly selected as controls for the subset analysis. Patients were stratified according to their MG onset age, thymic pathology and immunosuppressive treatment. Statistical analysis was performed by Fisher's exact test, asymptotic chi2 test, the two-sided Mann-Whitney test and Spearman's correlation coefficient. As a result, the 77C --> G mutation in exon 4 of the CD45 gene was found in 1 of 78 patients versus none of the 303 controls. Thus, no association was detected with this single nucleotide polymorphism in MG patients overall. Surprisingly, however, ratios of CD45RO+ to CD45RA+ T cells were lower among CD8+ T cells from patients with late-onset MG (P = 0.023). Thymoma patients also showed a similar trend among CD4+ and CD8+ T-cells, as expected. These differences were not related to immunosuppressive drug treatment or thymectomy (in the 67 informative patients). Since there is no other evidence for increased thymopoiesis in late-onset MG, we propose an altered subset balance in the circulation.

Cerebellar somatotopic representation and cerebro-cerebellar interconnections in ataxic patients.

Different methods of functional neuroimaging were used for studying somatotopic encoding of function in the cerebellum and for investigating cerebro-cerebellar interconnections in patients with cerebellar degeneration. fMRI showed, that the center of activation for hand function was located in the intermediate hemispheric portion of Larsell lobules H IV-V. Foot movements activated areas medial and anterior to the corresponding hand areas within Larsell lobules II-III. Changed function in motor cortices could be demonstrated in patients with cerebellar degeneration as compared to normal controls by recording movement-related cortical potentials (BP). In patients the motor potential was almost lacking and transcranial magnetic stimulation demonstrated enhancement of inhibitory mechanisms (prolonged postexcitatory inhibition) in the motor cortex. PET-findings suggested, that both effects are correlated to increased activity of inhibitory interneurons. Cerebellar patients showed increased activation in relation to movements in the SMA and basal ganglia and reduced activation in the cerebellum and lateral premotor areas. It could be speculated, that compensatory mechanisms are the reason for a stronger activation of the medial premotor system, including SMA, in patients with cerebellar degeneration. On the basis of our results it appears, that the cerebellum facilitates the lateral premotor system areas much more than it does the medial areas.

Enhancement of obliterative airway disease in rat tracheal allografts infected with recombinant rat cytomegalovirus.

BACKGROUND: Cytomegalovirus infection has been identified as a significant risk factor for the development of obliterative bronchiolitis in human lung transplant recipients. This study was designed to assess the influence of rat cytomegalovirus (RCMV) on the pathogenesis and development of obliterative bronchiolitis in an experimental model of obliterative airway disease, which occurs after allogenic heterotopic tracheal transplantation in rodents. METHODS: Sixty Lewis rats were infected intraperitoneally with 10(7) plaque-forming units of recombinant lac-Z-tagged RCMV expressing the gene for beta-galactosidase. Rats were either infected at the time of surgery (acute infection, n = 30) or 56 days before surgery (chronic infection, n = 30). Tracheae from Brown Norway (allograft) or Lewis (isograft) rats were implanted and wrapped in the greater omentum of infected Lewis rats. RCMV infection was verified in different recipient tissues by in vitro plaque-assays and by direct in situ staining for beta-galactosidase activity. The tracheal grafts were harvested on days 7, 14, and 21 after transplantation and stained with hematoxylin-eosin and Masson's trichrome. The peritracheal cellular inflammation was scored visually. The cellular density of the infiltrating cells and the extent of airway obliteration were analyzed by use of computer-digitized morphometry and compared with uninfected allografts as control. RESULTS: Both acute and chronic cytomegalovirus infection produced significantly higher mononuclear cell density values on days 7 and 14 compared with noninfected controls, indicating a more intense immune response in the infected allografts. Tracheal allograft obliteration was also more extensive after acute and, in particular, after chronic cytomegalovirus infection (64% narrowing after 21 days compared with 36% in grafts from noninfected control animals). CONCLUSIONS: Our experimental results provide direct evidence that the tracheal grafts were infected with RCMV and that the development of obliterative airway disease was enhanced in the acutely and chronically infected allografts compared with grafts from noninfected control animals.

Reevaluation of the Cottbus Reinfarction Study with 30 mg aspirin per day 4 years after the end of the study.

Four to 6 years after the end of the Cottbus Reinfarction Study with 30, 60 and 1000 mg/day aspirin, the survivors (72% of the patients) were reevaluated under standardized conditions at the district hospital. Nearly all patients (82%) of the former 30 mg group took further on 30 mg aspirin daily whereas of the former 1000 mg group only 20% continued to take doses higher than 500 mg aspirin. Forty-five percent changed to very low doses. Whereas the death rate was nearly the same in all three former dosage groups the total reinfarction rate was higher (22.5%) in the previous 1000 mg group in comparison to the 30 mg group (17.4%, p less than 0.05). The non-fatal reinfarction rate was by 50% lower in the former 30 mg group compared with the previous 1000 mg group. In the age group 50-59 a 8.6% non-fatal reinfarction rate is contrasted to 1.7% reinfarctions in patients of the former 30 mg group (p less than 0.01). The risk factors were not significantly different in the three groups.

Stanford experience with obliterative bronchiolitis after lung and heart-lung transplantation.

BACKGROUND: Obliterative bronchiolitis (OB) is the main chronic complication after heart-lung (HLTx) and lung transplantation (LTx), limiting the long-term success of both transplant procedures. METHODS: Since 1981, 135 HLTxs and 61 isolated LTxs were performed in 184 patients at Stanford University. RESULTS: The overall prevalence of OB in patients surviving longer than 3 months postoperatively was 64% after HLTx and 68% after LTx. The actuarial freedom from OB was 72%, 51%, 44%, and 29% at 1, 2, 3, and 5 years, respectively, after HLTx and LTx. An analysis of potential risk factors revealed that the frequency and severity of acute rejection episodes (p < 0.001) and the appearance of lymphocytic bronchiolitis on biopsy (p < 0.05) were significantly associated with the development of OB. With regard to diagnosis of OB, pulmonary function tests show early reductions of the forced expiratory flow between 25% and 75% of the forced vital capacity with subsequent decreases in the forced expiratory volume in 1 second. The sensitivity of transbronchial biopsies has increased to 71% since 1993. Current treatment consists of augmented immunosuppression. Concurrent acute rejection episodes or active OB on biopsy have been treated aggressively with high-dose steroid pulses. Analysis of data from 73 patients with OB after HLTx and LTx revealed actuarial 1-, 3-, 5-, and 10-year survival of 89%, 71%, 44%, and 17% versus 86%, 77%, 63% and 56% in patients without OB (p < 0.05 by log-rank analysis). The main complication and cause of death in patients with OB was superimposed respiratory tract infection, which was treated aggressively. CONCLUSIONS: Early diagnosis of OB using pulmonary function tests or transbronchial biopsy is possible and important, because immediate treatment initiation has led to acceptable survival rates, with nearly 50% of affected patients still alive 5 years after transplantation. Current experimental research on OB suggests that immune injury is the main pathogenetic event of airway obliteration in animal models; rapamycin and leflunomide are new immunosuppressive agents that may have the potential to prevent and treat airway obliteration.

Differential cerebellar activation related to perceived pain intensity during noxious thermal stimulation in humans: a functional magnetic resonance imaging study.

Little is known about the cerebellar involvement in pain processing in spite of the fact that the cerebellum probably plays a crucial role in pain-related behavior. Using functional magnetic resonance imaging we examined the differential cerebellar activation in 18 healthy subjects in relation to their perceived pain-intensity of noxious and non-noxious thermal stimuli. In contrast to non-noxious (40 degrees C) stimuli, noxious (48.5 degrees C) stimuli revealed activation in the deep cerebellar nuclei, anterior vermis and bilaterally in the cerebellar hemispheric lobule VI. With the same noxious stimulus (48.5 degrees C) there was differential cerebellar activation depending on the perceived pain intensity: high pain intensity ratings were associated with activation in ipsilateral hemispheric lobule III-VI, deep cerebellar nuclei and in the anterior vermis (lobule III). This differential cerebellar activation pattern probably reflects not only somatosensory processing but also perceived pain intensity that may be important for cerebellar modulation of nociceptive circuits.