A rat model of monitoring liver allograft rejection

Rat models are often used to study liver allograft rejection. We have established a model for rat liver allograft rejection, monitored by fine needle aspiration biopsy (FNAB), in the strain combination PVG-to-BN with a mean survival time of 37 ± 20 days. In this model, we observed acute rejection with an intense peak of lymphoid blasts and lymphocyte-dominated inflammation in the FNAB [9.1 ± 3.0 corrected increment units (CIU)], and an eventual increase in macrophages (up to 4.2 ± 4.4 CIU), together with fibrosis and parenchymal necrosis in the graft. Markers of immune activation, such as an increase in IL-2-receptor (from 1 % ± 2 % to 21 % ± 13 %) and class II (from 20 % ± 9 % to 43 % ± 13 %) expressing lymphoid cells and induction of ICAM-1 in the graft, were consistent with the overall cellular response. The FNAB correlated well with parallel graft histology. In this rat model, the atraumatic monitoring makes a close follow-up possible without having to sacrifice the experimental animals. This saves work, animals, and costs in the study of liver rejection. Received: 2 July 1996 Accepted: 28 October 1996     

BK polyomavirus-associated hemorrhagic cystitis among pediatric allogeneic bone marrow transplant recipients: Treatment response and evidence for nosocomial transmission

BackgroundBK polyomavirus-associated hemorrhagic cystitis (BK-PyVHC) is a significant complication of allogenic hematopoietic stem cell transplantation (HSCT), but risk factors and treatment are currently unresolved. BK-PyVHC typically presents with clinical cystitis, macrohematuria, and increasing urine and blood BKV loads.ObjectivesCharacterization of children undergoing allogeneic HSCT with BK-PyVHC and their clinical and antibody response to cidofovir treatment.Study designBy prospective screening of urine and plasma in 50 pediatric allogenic HSCT performed between 2008 and 2010, we identified 6 (12%) children with BK-PyVHC. Cidofovir was administered intravenously to 5 patients and intravesically to 4 patients (3 double treatments).ResultsDecreasing BKV viremia of > 2 log₁₀ copies/mL and clinical resolution was seen in 4 patients over 5–12 weeks. Responses occurred only in patients mounting BKV-specific IgM and IgG responses. Epidemic curve plots, BKV genotyping and contact tracing provided evidence of transmission between 2 BKV-seronegative patients, but ruled out transmission among the remaining four patientsConclusionsThe data suggest that BK-PyVHC may be the result of nosocomial transmission in children with low/undetectable BKV antibodies and raises urgent questions about appropriate infection control measures and the role of cidofovir.     

Effects of tissue-engineered articular disc implants on the biomechanical loading of the human temporomandibular joint in a three-dimensional finite element model

The purpose of this study was to evaluate biomechanical loading of the temporomandibular joint when using a biodegradable laminate implant to replace the articular disc and to test the hypothesis that the use of the implant reduces stress distribution in the condyle, implant, and glenoid fossa. A finite element model of a female human mandible, including the temporomandibular joint, which had two standard endosseous implants inserted bilaterally in the premolar region, was constructed from computed tomography scan images using a commercially available finite element software. The disc, condyle, and glenoid fossa were arbitrarily divided into five regions: the anterior, posterior, medial, lateral, and central. The disc was then replaced with a poly-L/DL-lactide biodegradable laminate. The finite element model was then used to predict principal and Von Mises stresses. The use of poly-L/DL-lactide implant resulted in remarkable reduction in Von Mises stresses (approximately threefold) in the anterior, central, and medial regions of the mandibular condyle in comparison with slight to moderate stress reductions in the corresponding regions of the implant and glenoid fossa. The mandibular condyle also demonstrated the largest total displacement in all directions followed by the implant and glenoid fossa. The use of an alloplastic implant such as the bioresorbable, poly-L/DL-lactide laminate to replace the articular disc reduces loading of the mandibular condyle rather than the implant and glenoid fossa. These findings lead to support the hypothesis that the mandibular condyle more likely functions as a shock absorber than the disc. The use of bioresorbable laminate implants might prove an efficient technique to replace the articular disc and promote normal function of the temporomandibular joint.     

Influence of Body Mass Index and Smoking on the Long-Term Survival of Patients With Renal Cell Cancer

BackgroundSmoking and obesity are known risk factors for renal cell carcinoma (RCC). We determined the influence of smoking, body mass index (BMI), and symptoms on the survival of patients with RCC.Patients and MethodsIn this retrospective study, the relative overall survival (OS) up to 25 years was calculated among 948 Finnish patients with RCC diagnosed between 1964 and 1997 using a Bayesian univariate analysis and the life-table method.ResultsObese patients had better OS than did normal or underweight patients (median, 5.9 years, 3.4 years, and 12 months, respectively), with lower stage and more asymptomatic tumors at diagnosis and fewer relapses during surveillance. Clinical presentation of the tumor was a stronger prognostic factor than BMI; however, asymptomatic patients with a low BMI had poorer survival compared with normal or overweight patients. There was no difference in tumor stage or presentation at diagnosis between the nonsmokers and smokers; however, the smokers had more relapses with shorter disease-free intervals (DFIs) than did the nonsmokers. The OS was poorer in the smokers (4.2 years compared with 6.6 years in nonsmokers), but no difference was observed in cancer-specific survival (CSS).ConclusionOverweight patients have better survival, with more asymptomatic or local tumors. The clinical presentation was a stronger prognostic factor than BMI. Additionally, survival is poorer in smokers, even if there is no difference in tumor stage or symptoms.     

Loss of cutaneous microbial diversity during first 3 weeks of life in very low birthweight infants

Neonatal sepsis (NS) is a frequent problem in neonatal intensive care, especially in preterm and very low birthweight (VLBW) infants. The objective of the study was to characterize the cutaneous bacterial microbiome in VLBW infants treated in the neonatal intensive care unit (NICU). Non‐invasive skin microbiome specimens were taken repeatedly from 12 VLBW infants during treatment in NICU starting on the first day of life. All infants received benzylpenicillin and netilmicin during the first 1‐5 postnatal days. Samples were also collected from incubators. High cutaneous microbial diversity was present at birth in 11 of 12 of the infants, but the diversity decreased substantially after the first weeks of life in all infants regardless of their infection status. After the loss of diversity, one Staphylococcus operational taxonomic unit dominated the skin microbiome. Recovery of microbial diversity was seen in six of 12 neonates. The microbiome of incubators showed typical environmental bacterial genera. Maternal antibiotic treatment, the aetiology of the preterm birth or being born by C‐section did not appear to affect the diversity of skin microbiota at birth, and no correlation was found between cutaneous microbiome and NS.     

Drowning in Finland: "external cause" and "injury" codes.

BACKGROUND: The International Classification of Diseases (ICD) external codes (E codes) for drowning assist in determining the primary event leading to drowning, but do not alone allow the precise determination of the overall drowning rates. AIMS: To analyze the sensitivity of the ICD E codes for drowning. To describe the pattern and trend of drowning deaths that are classified with E codes other than for drowning. SETTING: Finland, 1969-2000. METHODS: Mortality files of Statistics Finland were searched electronically using the injury codes (I codes) and E codes for drowning. Cross analysis of I and E coded drownings was performed to determine the rate and pattern of drowning cases classified with E codes other than for drowning. Time trends were calculated using the Poisson regression model. RESULTS: Of 13 705 drowning deaths, 644 (4.7%) were not identified with the E codes for drowning. The great majority (n=547, 84.9%) of these cases were traffic accidents resulting in drowning. No significant time trends were found even after the introduction, in 1996, of the ICD 10th revision. CONCLUSIONS: In Finland, underestimation of overall drowning rates using the E code alone is less pronounced than in countries where similar studies have been performed. The relatively high rate of transport accidents resulting in drowning indicates a specific target for preventive countermeasures.     

Infection of mice with Nematospiroides dubius: demonstration of neutrophil-mediated immunity in vivo in the presence of antibodies

The ability of murine neutrophils to confer resistance to mice against infection by the helminth parasite Nematospiroides dubius has been investigated. Mice whose neutrophils had been 'altered' by an immunizing infection with third-stage larvae (L3) of N. dubius exhibited resistance to a challenge dose of L3 given 4 days after the immunizing infection, provided greater than 0.1 ml of immune mouse serum was passively transferred within 0-24 hr of challenge. Normal mouse serum was ineffective, as was immune serum given at the time of challenge to naive (unimmunized) mice. Neutrophils purified from the blood of mice infected 4 days previously were able to reduce the infectivity of exsheathed L3 when incubated with the latter in vitro in the presence of fresh immune serum. In contrast, peritoneal exudate cells collected at the same time were inactive in this test, indicating that activated macrophages capable of damaging L3 were not yet present and that the immunity of 4-day infected mice given immune serum was probably attributable to the presence of 'altered' neutrophils. The capacity of neutrophils to confer resistance to infection in vivo was unambiguously demonstrated by the passive transfer of 98 +/- 4% pure neutrophils, isolated from the blood of 4-day infected (C57Bl X BALB/c)F1 mice, to uninfected F1 mice. Only those mice which received both neutrophils and immune serum exhibited resistance to a challenge infection. In contrast, mice injected with an eosinophil-enriched cell preparation and immune serum were not resistant. These results indicate for the first time that neutrophils have the capacity to damage nematode parasites in vivo and that they are active against N. dubius in mice infected with this parasite.     

Prevention of zoonotic animal diseases: a step towards co-operation among Nordic authorities?

Aim  

With globalisation, the spreading and consequences of serious animal diseases will become an increasingly realistic threat, also to Nordic countries, their food animals and consumers. It has already been suggested that it might be useful to establish an army to manage all co-operations among countries, for instance, for medical co-operation needs. In light of this, it might also be important to guarantee the security of animal products and to fight together against animal diseases, some of which are potentially dangerous for human beings. The aim of this study was to investigate how the laws concerning animal diseases construct the reality of co-operation among authorities in different Nordic countries.