Risk of brainstem necrosis in pediatric patients with central nervous system malignancies after pencil beam scanning proton therapy.

Background: Radiation therapy (RT) plays an important role in management of pediatric central nervous system (CNS) malignancies. Centers are increasingly utilizing pencil beam scanning proton therapy (PBS-PT). However, the risk of brainstem necrosis has not yet been reported. In this study, we evaluate the rate of brainstem necrosis in pediatric patients with CNS malignancies treated with PBS-PT.Material and methods: Pediatric patients with non-hematologic CNS malignancies treated with PBS-PT who received dose to the brainstem were included. All procedures were approved by the institutional review board. Brainstem necrosis was defined as symptomatic toxicity. The actuarial rate was analyzed by the Kaplan Meier method.Results: One hundred and sixty-six consecutive patients were reviewed. Median age was 10 years (range 0.5-21 years). Four patients (2.4%) had prior radiation. Median maximum brainstem dose in the treated course was 55.4 Gy[RBE] (range 0.15-61.4 Gy[RBE]). In patients with prior RT, cumulative median maximum brainstem dose was 98.0 Gy [RBE] (range 17.0-111.0 Gy [RBE]). Median follow up was 19.6 months (range, 2.0-63.0). One patient who had previously been treated with twice-daily radiation therapy and intrathecal (IT) methotrexate experienced brainstem necrosis. The actuarial incidence of brainstem necrosis was 0.7% at 24 months (95% CI 0.1-5.1%).Conclusion: The rate of symptomatic brainstem necrosis was extremely low after treatment with PBS-PT in this study. Further work to clarify clinical and dosimetric parameters associated with risk of brainstem necrosis after PBS-PT is needed.

Characterization of resident lymphocytes in human pancreatic islets.

The current view of type 1 diabetes (T1D) is that it is an immune-mediated disease where lymphocytes infiltrate the pancreatic islets, promote killing of beta cells and cause overt diabetes. Although tissue resident immune cells have been demonstrated in several organs, the composition of lymphocytes in human healthy pancreatic islets have been scarcely studied. Here we aimed to investigate the phenotype of immune cells associated with human islets of non-diabetic organ donors. A flow cytometry analysis of isolated islets from perfused pancreases (n = 38) was employed to identify alpha, beta, T, natural killer (NK) and B cells. Moreover, the expression of insulin and glucagon transcripts was evaluated by RNA sequencing. Up to 80% of the lymphocytes were CD3+ T cells with a remarkable bias towards CD8+ cells. Central memory and effector memory phenotypes dominated within the CD8+ and CD4+ T cells and most CD8+ T cells were positive for CD69 and up to 50-70% for CD103, both markers of resident memory cells. The frequency of B and NK cells was low in most islet preparations (12 and 3% of CD45+ cells, respectively), and the frequency of alpha and beta cells varied between donors and correlated clearly with insulin and glucagon mRNA expression. In conclusion, we demonstrated the predominance of canonical tissue resident memory CD8+ T cells associated with human islets. We believe that these results are important to understand more clearly the immunobiology of human islets and the disease-related phenotypes observed in diabetes.

Use of Swedish smokeless tobacco (snus) and the risk of Type 2 diabetes and latent autoimmune diabetes of adulthood (LADA).

AIMS: It has been suggested that moist snuff (snus), a smokeless tobacco product that is high in nicotine and widespread in Scandinavia, increases the risk of Type 2 diabetes. Previous studies are however few, contradictory and, with regard to autoimmune diabetes, lacking. Our aim was to study the association between snus use and the risk of Type 2 diabetes and latent autoimmune diabetes of adulthood (LADA). METHOD: Analyses were based on incident cases (Type 2 diabetes, n = 724; LADA, n = 200) and population-based controls (n = 699) from a Swedish case-control study. Additional analyses were performed on cross-sectional data from the Norwegian HUNT study (n = 21 473) with 829 prevalent cases of Type 2 diabetes. Odds ratios (OR) were estimated adjusted for age, BMI family history of diabetes and smoking. Only men were included. RESULTS: No association between snus use and Type 2 diabetes or LADA was seen in the Swedish data. For Type 2 diabetes, the OR for > 10 box-years was 1.00 [95% confidence interval (CI), 0.47 to 2.11] and for LADA 1.01 (95% CI, 0.45 to 2.29). Similarly, in HUNT, the OR for Type 2 diabetes in ever-users was estimated at 0.91 (95% CI, 0.75 to 1.10) and in heavy users at 0.92 (95% CI, 0.46 to 1.83). CONCLUSION: The risk of Type 2 diabetes and LADA is unrelated to the use of snus, despite its high nicotine content. This opens the possibility of the increased risk of Type 2 diabetes seen in smokers may not be attributed to nicotine, but to other substances in tobacco smoke.

IFNγ and perforin cooperate to control infection and prevent fatal pathology during persistent gammaherpesvirus infection in mice.

Infection with murine gammaherpesvirus 68 has become an accepted model for studying the virus/host interactions with regard to gammaherpesvirus infections. Previous studies using gene-deficient mice have revealed that neither IFNγ nor perforin is essential in controlling the outcome of infection or the virus load during chronic infection in C57BL/6 mice. However, pronounced multiorgan fibrosis and splenic atrophy are observed in mice lacking IFNγ or the IFNγ receptor. To study the interplay between perforin and IFNγ in controlling the virus-induced pathology and the viral load during chronic gammaherpesvirus infection, we infected IFNγ/perforin double-deficient C57BL/6 mice and followed the course of infection. While absence of perforin prevented the splenic atrophy in IFNγ-deficient mice, fibrosis did not disappear. Moreover, double-deficient mice developed extreme splenomegaly, were unable to control the viral load and displayed chronic immune activation. Thus, IFNγ and perforin act in concert to minimize pathology and control the viral load in mice chronically infected with MHV68. Furthermore, while certain aspect of the virus-induced pathology in IFNγ-deficient mice may be alleviated in double-deficient mice, other aspects are exaggerated, and the normal architecture of the spleen is completely destroyed. We believe that these findings add to the understanding of the virus/host interaction during chronic gammaherpes virus infection.

Coffee consumption and the risk of latent autoimmune diabetes in adults--results from a Swedish case-control study.

AIMS: Coffee consumption is associated with a reduced risk of Type 2 diabetes. Our aim was to investigate if coffee intake may also reduce the risk of latent autoimmune diabetes in adults, an autoimmune form of diabetes with features of Type 2 diabetes. METHODS: We used data from a population-based case-control study with incident cases of adult onset (≥ 35 years) diabetes, including 245 cases of latent autoimmune diabetes in adults (glutamic acid decarboxylase antibody positive), 759 cases of Type 2 diabetes (glutamic acid decarboxylase antibody negative), together with 990 control subjects without diabetes, randomly selected from the population. Using questionnaire information on coffee consumption, we estimated the odds ratio of latent autoimmune diabetes in adults and Type 2 diabetes adjusted for age, sex, BMI, smoking, physical activity, alcohol, education and family history of diabetes. RESULTS: Coffee intake was inversely associated with Type 2 diabetes (odds ratio 0.92, 95% CI 0.87-0.98 per cup/day). With regard to latent autoimmune diabetes in adults, the general trend was weak (odds ratio 1.04, 95% CI 0.96-1.13), but stratification by degree of autoimmunity (median glutamic acid decarboxylase antibody levels) suggested that coffee intake may be associated with an increased risk of high glutamic acid decarboxylase antibody latent autoimmune diabetes in adults (odds ratio 1.11, 95% CI 1.00-1.23 per cup/day). Furthermore, for every additional cup of coffee consumed per day, there was a 15.2% (P = 0.0268) increase in glutamic acid decarboxylase antibody levels. CONCLUSIONS: Our findings confirm that coffee consumption is associated with a reduced risk of Type 2 diabetes. Interestingly, the findings suggest that coffee may be associated with development of autoimmunity and possibly an increased risk of more Type 1-like latent autoimmune diabetes in adults.

Diagnostic accuracy of CBCT for periodontal lesions.

OBJECTIVES: The present study compares the diagnostic value of periodontal bone defect images using conventional two-dimensional single-tooth radiographs and three-dimensional cone beam computed tomography (CBCT) images. MATERIALS AND METHODS: Classified periodontal bone defects were prepared on pig mandibles and presented radiographically. Fifteen dentists were instructed to make a diagnosis based on these x-rays, regarding the type and the extent of the bone defects. Subsequently, the results were evaluated and compared to the morphology of the surgically prepared defects as the gold standard. RESULTS: On average, the diagnosis of infrabony defects were 21 %, dehiscence 25 %, and fenestration 33 % more accurate using the three-dimensional projection than with the single-tooth radiograph. Furthermore, the CBCT allows grade II furcation to be captured more accurately. CONCLUSIONS: The results of this study indicate that a considerably more precise analysis of periodontal defects is possible due to the third dimension. Particularly, in the oro-vestibular orientation, defects could be detected significantly more accurate. CLINICAL RELEVANCE: CBCT images offer an advantageous alternative to the conventional single-tooth radiograph while taking the higher exposure of radiation into account.

Transdiscal instrumentation in single-level lumbosacral fusion for high-grade isthmic pediatric spondylolisthesis: Technical note and review of the literature.

Pediatric spondylolisthesis is a common cause of back pain in children, typically managed conservatively with bracing and non-steroidal anti-inflammatory drugs. When posterolateral fusion is performed for refractory pain, pseudarthrosis and implant failure may occur, necessitating reoperation. To improve patient outcomes, there is a need for alternative surgical techniques to effectively manage high-grade isthmic slips. Here, the authors report the case of a child with Meyerding grade III anterolisthesis of L5 on S1 who was treated with a single-level, instrumented fusion using bilateral S1-L5 transdiscal screws, supported with L5-S1 posterolateral instrumentation and arthrodesis. Postoperatively, there was improvement in the patient's symptoms with good clinical and radiographic outcomes. The patient continues to be symptom free with radiographic evidence of hardware stability and bony fusion across the segment. The authors detail a novel surgical technique in children as well as a review of lumbosacral transdiscal screw fixation. Further evidence is required to definitively establish the safety, outcomes, and biomechanical strength of this technique.

Roundabout model with on-ramp queues: Exact results and scaling approximations.

This paper introduces a general model of a single-lane roundabout, represented as a circular lattice that consists of L cells, with Markovian traffic dynamics. Vehicles enter the roundabout via on-ramp queues that have stochastic arrival processes, remain on the roundabout a random number of cells, and depart via off-ramps. Importantly, the model does not oversimplify the dynamics of traffic on roundabouts, while various performance-related quantities (such as delay and queue length) allow an analytical characterization. In particular, we present an explicit expression for the marginal stationary distribution of each cell on the lattice. Moreover, we derive results that give insight on the dependencies between parts of the roundabout, and on the queue distribution. Finally, we find scaling limits that allow, for every partition of the roundabout in segments, to approximate (i) the joint distribution of the occupation of these segments by a multivariate Gaussian distribution, and (ii) the joint distribution of their total queue lengths by a collection of independent Poisson random variables. To verify the scaling limit statements, we develop a way to empirically assess convergence in distribution of random variables.

Clinical outcomes after treatment of intra-bony defects with an EMD/synthetic bone graft or EMD alone: a multicentre randomized-controlled clinical trial.

OBJECTIVES: Comparison of the outcomes of a combination of an enamel matrix derivative and a synthetic bone graft (EMD/SBC) with EMD alone in wide intra-bony defects. MATERIAL AND METHODS: Seventy-three patients with chronic periodontitis were recruited in five centres in Germany. All patients had one wide intra-bony defect of >/=4 mm. Surgical procedures involved microsurgical technique and the modified papilla preservation flap. After debridement, defects were randomly assigned to EMD/SBC (test) or EMD (control). Assessments at baseline and after 6 months included bone sounding, attachment levels, probing pocket depths, bleeding on probing and recessions. Early wound-healing, adverse effects and patients' perceptions were also recorded. RESULTS: Both treatment modalities led to significant clinical improvements. Change in bone fill 6 months after surgery was 2.0 mm (+/- 2.1) in the test group and 2.1 mm (+/- 1.2) in the control group. A gain in clinical attachment of 1.3 mm (+/- 1.8) in the test group and 1.8 mm (+/- 1.6) in the control group was observed. One week after surgery, primary closure was maintained in 95% of the test sites and 100% of the control sites. No differences in patients' perceptions were found. CONCLUSION: The results of the present study showed similar clinical outcomes following both treatment modalities.

Full-mouth disinfection for the treatment of adult chronic periodontitis.

BACKGROUND: In an attempt to enhance treatment outcomes, alternative protocols for anti-infective periodontal therapy have been introduced. OBJECTIVES: To evaluate the effectiveness of full-mouth disinfection or full-mouth scaling compared to conventional quadrant scaling for periodontitis. SEARCH STRATEGY: Data sources included electronic databases, handsearched journals and contact with experts. The Cochrane Oral Health Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE were searched. Reference lists from relevant articles were scanned and the authors of eligible studies were contacted to identify trials and obtain additional information. Date of most recent searches: December 2006: (CENTRAL) (The Cochrane Library 2006, Issue 4). SELECTION CRITERIA: Randomised controlled trials were selected with at least 3 months follow up comparing full-mouth scaling and root planing within 24 hours with (FMD) or without (FMS) the adjunctive use of an antiseptic (chlorhexidine) with conventional quadrant scaling and root planing (control). The methodological quality of the studies was assessed within the data extraction form, mainly focusing on: method of randomisation, allocation concealment, blindness of examiners and completeness of follow up. DATA COLLECTION AND ANALYSIS: Data extraction and quality assessment were conducted independently by multiple review authors. The primary outcome measure was tooth loss, secondary outcomes were reduction of probing depth, bleeding on probing and gain in probing attachment. The Cochrane Collaboration statistical guidelines were followed. MAIN RESULTS: The search identified 216 abstracts. Review of these abstracts resulted in 12 publications for detailed review. Finally, seven randomised controlled trials (RCTs) which met the criteria for eligibility were independently selected by two review authors. None of the studies included reported on tooth loss. All treatment modalities led to significant improvements in clinical parameters after a follow up of at least 3 months. For the secondary outcome, reduction in probing depth, the mean difference between FMD and control was 0.53 mm (95% confidence interval (CI) 0.28 to 0.77) in moderately deep pockets of single rooted teeth and for gain in probing attachment 0.33 mm (95% CI 0.04 to 0.62) in moderately deep single and multirooted teeth. Comparing FMD and FMS the mean difference in one study for gain in probing attachment amounted to 0.74 mm in favour of FMS (95% CI 0.17 to 1.31) for deep pockets in multirooted teeth, while another study reported a mean difference for reduction in bleeding on probing of 18% in favour of FMD (95% CI -33.74 to -2.26) for deep pockets of single rooted teeth. No significant differences were observed for any of the outcome measures, when comparing FMS and control. AUTHORS' CONCLUSIONS: In patients with chronic periodontitis in moderately deep pockets slightly more favourable outcomes for pocket reduction and gain in probing attachment were found following FMD compared to control. However, these additional improvements were only modest and there was only a very limited number of studies available for comparison, thus limiting general conclusions about the clinical benefit of full-mouth disinfection.

CRAF gene fusions in pediatric low-grade gliomas define a distinct drug response based on dimerization profiles.

Pediatric low-grade gliomas (PLGGs) are commonly associated with BRAF gene fusions that aberrantly activate the mitogen-activated protein kinase (MAPK) signaling pathway. This has led to PLGG clinical trials utilizing RAF- and MAPK pathway-targeted therapeutics. Whole-genome profiling of PLGGs has also identified rare gene fusions involving another RAF isoform, CRAF/RAF1, in PLGGs and cancers occuring in adults. Whereas BRAF fusions primarily dysregulate MAPK signaling, the CRAF fusions QKI-RAF1 and SRGAP3-RAF1 aberrantly activate both the MAPK and phosphoinositide-3 kinase/mammalian target of rapamycin (PI3K/mTOR) signaling pathways. Although ATP-competitive, first-generation RAF inhibitors (vemurafenib/PLX4720, RAFi) cause paradoxical activation of the MAPK pathway in BRAF-fusion tumors, inhibition can be achieved with 'paradox breaker' RAFi, such as PLX8394. Here we report that, unlike BRAF fusions, CRAF fusions are unresponsive to both generations of RAFi, vemurafenib and PLX8394, highlighting a distinct responsiveness of CRAF fusions to clinically relevant RAFi. Whereas PLX8394 decreased BRAF-fusion dimerization, CRAF-fusion dimerization is unaffected primarily because of robust protein-protein interactions mediated by the N-terminal non-kinase fusion partner, such as QKI. The pan-RAF dimer inhibitor, LY3009120, could suppress CRAF-fusion oncogenicity by inhibiting dimer-mediated signaling. In addition, as CRAF fusions activate both the MAPK and PI3K/mTOR signaling pathways, we identify combinatorial inhibition of the MAPK/mTOR pathway as a potential therapeutic strategy for CRAF-fusion-driven tumors. Overall, we define a mechanistic distinction between PLGG-associated BRAF- and CRAF/RAF1 fusions in response to RAFi, highlighting the importance of molecularly classifying PLGG patients for targeted therapy. Furthermore, our study uncovers an important contribution of the non-kinase fusion partner to oncogenesis and potential therapeutic strategies against PLGG-associated CRAF fusions and possibly pan-cancer CRAF fusions.

Family history of type 1 and type 2 diabetes and risk of latent autoimmune diabetes in adults (LADA).

BACKGROUND: A family history of diabetes (FHD) is a strong predictor of diabetes risk, yet has rarely been investigated in latent autoimmune diabetes in adults (LADA). This study therefore investigated the risk of LADA and type 2 diabetes (T2D) in relation to FHD, taking into account the type of diabetes in relatives. METHODS: Data from a population-based study were used, including incident cases of LADA [glutamic acid decarboxylase antibody (GADA)-positive, n=378] and T2D (GADA-negative, n=1199), and their matched controls (n=1484). First-degree relatives with disease onset at age<40 years and taking insulin treatment were classified as type 1 diabetes (T1D) or, if otherwise, as T2D. Odds ratios (ORs) were adjusted for age, gender, BMI, education and smoking. Cases were genotyped for high- and low-risk HLA genotypes. RESULTS: Both FHD-T1D (OR: 5.8; 95% CI: 3.2-10.3) and FHD-T2D (OR: 1.9; 95% CI: 1.5-2.5) were associated with an increased risk of LADA, whereas the risk of T2D was associated with FHD-T2D (OR: 2.7; 95% CI: 2.2-3.3), but not FHD-T1D. In LADA patients, FHD-T1D vs FHD-T2D was associated with higher GADA but lower C-peptide levels, lower prevalence of low-risk HLA genotypes (5.0% vs 28.6%, respectively; P=0.038) and a tendency for higher prevalence of high-risk genotypes (90.0% vs 69.1%, respectively; P=0.0576). CONCLUSION: The risk of LADA is substantially increased with FHD-T1D but also, albeit significantly less so, with FHD-T2D. This supports the idea of LADA as a mix of both T1D and T2D, but suggests that the genes related to T1D have greater impact. LADA patients with FHD-T1D had more T1D-like features, emphasizing the heterogeneity of LADA.

Cartilage oligomeric matrix protein contributes to the development and metastasis of breast cancer.

Cartilage oligomeric matrix protein (COMP) is a soluble pentameric protein expressed in cartilage and involved in collagen organization. Tissue microarrays derived from two cohorts of patients with breast cancer (n=122 and n=498) were immunostained, revealing varying expression of COMP, both in the tumor cells and surrounding stroma. High levels of COMP in tumor cells correlated, independently of other variables, with poor survival and decreased recurrence-free survival. Breast cancer cells, MDA-MB-231, stably expressing COMP were injected into the mammary fat pad of SCID (CB-17/Icr-Prkdcscid/Rj) mice. Tumors expressing COMP were significantly larger and were more prone to metastasize as compared with control, mock-transfected, tumors. In vitro experiments confirmed that COMP-expressing cells had a more invasive phenotype, which could in part be attributed to an upregulation of matrix metalloprotease-9. Furthermore, microarray analyses of gene expression in tumors formed in vivo showed that COMP expression induced higher expression of genes protecting against endoplasmic reticulum stress. This observation was confirmed in vitro as COMP-expressing cells showed better survival as well as a higher rate of protein synthesis when treated with brefeldin A, compared with control cells. Further, COMP-expressing cells appeared to undergo a metabolic switch, that is, a Warburg effect. Thus, in vitro measurement of cell respiration indicated decreased mitochondrial metabolism. In conclusion, COMP is a novel biomarker in breast cancer, which contributes to the severity of the disease by metabolic switching and increasing invasiveness and tumor cell viability, leading to reduced survival in animal models and human patients.

Long-term persistence of Coxiella burnetii after acute primary Q fever.

BACKGROUND: Long-term persistence of C. burnetii in infected animals was established in the 1950s and 60s, but the implications for human Q fever are not fully explored. AIM: To compare the prevalence of markers of infection in a cohort of Q fever patients in Australia (up to 5 years after infection) with those in the 1989 Birmingham cohort (12 years after infection). DESIGN: Case follow-up study. METHODS: C. burnetii was tested for by: (i) antibodies to Phase 1 and 2 antigens in the three immunoglobulin classes; (ii) detection of DNA in bone marrow and peripheral blood mononuclear cells by PCR assays directed against several different targets in the genome; and (iii) attempts to isolate coxiellas in cell culture or mice from PCR-positive samples. Amplicon specificity was verified by fluorometric probing and by sequencing. Cross-contamination was excluded by extensive use of non-template controls, and in particular by the use of certain IS1111a target sequences. RESULTS: Irrespective of clinical state, both groups remained seropositive, principally exhibiting medium levels of IgG antibody against C. burnetii Phase 2 antigen. C. burnetii genomic DNA was detected by PCR in 65% of bone marrow aspirates from Australian patients and approximately 88% of Birmingham patients. No coxiella were isolated from PCR positive samples. DISCUSSION: We propose a provisional model for persistence. In Q fever without sequelae, the process is largely confined to the bone marrow. In Q fever fatigue syndrome (QFS), it is modulated by the patient's immunogenetic background to give higher levels of coxiella genomes in bone marrow and increased shedding into the peripheral blood. In Q fever endocarditis, late pregnancy, or during iatrogenic or other immunosuppression, the multiplication cycle is prolonged, and a potential source of live organisms.

Altered serotonin (5-HT) 1D and 2A receptor expression may contribute to defective insulin and glucagon secretion in human type 2 diabetes.

Islet produced 5-hydroxy tryptamine (5-HT) is suggested to regulate islet hormone secretion in a paracrine and autocrine manner in rodents. Hitherto, no studies demonstrate a role for this amine in human islet function, nor is it known if 5-HT signaling is involved in the development of beta cell dysfunction in type 2 diabetes (T2D). To clarify this, we performed a complete transcriptional mapping of 5-HT receptors and processing enzymes in human islets and investigated differential expression of these genes in non-diabetic and T2D human islet donors. We show the expression of fourteen 5-HT receptors as well as processing enzymes involved in the biosynthesis of 5-HT at the mRNA level in human islets. Two 5-HT receptors (HTR1D and HTR2A) were over-expressed in T2D islet donors. Both receptors (5-HT1d and 5-HT2a) were localized to human alpha, beta and delta cells. 5-HT inhibited both insulin and glucagon secretion in non-diabetic islet donors. In islets isolated from T2D donors the amine significantly increased release of insulin in response to glucose. Our results suggest that 5-HT signaling participates in regulation of overall islet hormone secretion in non- diabetic individuals and over-expression of HTR1D and HTR2A may either contribute to islet dysfunction in T2D or arise as a consequence of an already dysfunctional islet.

Reconstructive challenges in the extended endoscopic transclival approach.

OBJECTIVE: We wanted to present our experience with the extended endoscopic approach to clival pathology, focusing on cerebrospinal fluid leak and reconstruction challenges. METHODS: We examined a consecutive series of 37 patients undergoing the extended endoscopic approach for skull base tumours, 9 patients with clival pathology. Patients were examined for the incidence of post-operative cerebrospinal fluid leak in relation to tumour pathology, location, size, reconstruction and lumbar drain. RESULTS: The overall incidence of post-operative cerebrospinal fluid leak was 10.8 per cent. Seventy-five per cent of patients who had a post-operative cerebrospinal fluid leak underwent a transclival approach (p < 0.05). All patients with clival pathology who underwent an intradural dissection had a post-operative cerebrospinal fluid leak (p < 0.05). CONCLUSION: Post-operative cerebrospinal fluid leak rates after the extended endoscopic approach have improved significantly after advancements including the vascularised nasoseptal flap. Despite this, transclival approaches continue to pose much difficulty. Further investigation is necessary to develop technical improvements that can meet the unique challenges associated with this region.

Cytokine dysregulation in the post-Q-fever fatigue syndrome.

The post-Q-fever fatigue syndrome (QFS) (inappropriate fatigue, myalgia and arthralgia, night sweats, changes in mood and sleep patterns) follows about 20% of laboratory-proven, acute primary Q-fever cases. Cytokine dysregulation resulting from chronic immune stimulation and modulation by persistence of Coxiella burnetii cells or their antigens is hypothesized. We studied cytokine release patterns of peripheral blood mononuclear cells (PBMC) stimulated with various ligands in short-term culture, from 18 patients with active QFS, and 27 controls: six with resolving QFS, five who had had acute primary Q-fever without subsequent QFS, eight healthy Q-fever vaccinees and eight healthy subjects without Q-fever antibody. Conditioned media (CM) from PBMC stimulated in short-term culture with Q-fever antigens, PHA or measles antigen (as an unrelated antigen) were assayed for IL-2, IL-4, IL-5, IL-6, IL-10 and IFN gamma by AgEIA, and for IL-1 and TNF alpha/beta by bioassay. Aberrant cytokine release patterns were observed with PBMC from QFS patients when stimulated with Q-fever antigens: an accentuated release of IL-6 which was significantly [p = 0.01, non-parametric one-way analysis of variance (ANOVA)] in excess of medians for all four control groups. With IL-2, the number of responders in the active QFS group was decreased relative to control groups (Fisher's exact test, p = 0.01) whereas the number of IFN gamma responders was increased (Fisher's exact test, p = 0.0008). Significant correlations were observed between concentrations of IL-6 in CM, total symptom scores, and scores for other key symptoms.

Reversible posterior leukoencephalopathy occurring during resection of a posterior fossa tumor: case report and review of the literature.

OBJECTIVE AND IMPORTANCE: Our goal was to present a clinically and radiographically documented case of reversible posterior leukoencephalopathy (RPL) that occurred during resection of a posterior fossa tumor. Although RPL has been previously described in multiple nonsurgical settings, we hope that this case description makes RPL more clinically and radiographically recognizable to neurosurgeons. CLINICAL PRESENTATION: RPL is the clinical syndrome of headaches, altered mental status, seizures, and visual loss, with radiographic findings of reversible parieto-occipital changes on cerebral computed tomographic and magnetic resonance imaging scans. It has been previously reported in the settings of malignant hypertension, renal disease, eclampsia, and immunosuppression. To our knowledge, the patient presented represents the first clinically and radiographically documented case of RPL occurring during resection of a posterior fossa tumor. The patient intraoperatively exhibited wide fluctuations in blood pressure and awoke with clinical and radiographic findings consistent with RPL. INTERVENTION: Aggressive intraoperative and postoperative management of the patient's blood pressure, supportive intensive care, rehabilitation, and close radiographic follow-up were performed. CONCLUSION: RPL can occur as a result of intraoperative variations in blood pressure, even among young, previously healthy individuals. With the aforementioned interventions, the patient experienced significant clinical and radiographic recovery.

A test in vero cell monolayers for toxin production by strains of Pasteurella multocida isolated from pigs suspected of having atrophic rhinitis.

Monolayers of Vero cells showed a morphological change after exposure to supernatants of certain porcine Pasteurella multocida cultures. It appeared possible to screen Pasteurella multocida isolates for their ability to produce toxin and to cause atrophic rhinitis in pigs. A close correlation with the guinea pig skin test was demonstrated.

Efficacy of a trivalent Haemophilus paragallinarum vaccine compared to bivalent vaccines.

The efficacy of a trivalent oil-adjuvant Coryza vaccine containing serotypes A, B and C of Haemophilus paragallinarum has been compared with that of a bivalent oil-adjuvant Coryza vaccine containing serotypes A and C and that of a commercially available, bivalent A1(OH)3-potentiated vaccine, containing types A and C. The trivalent vaccine, given at 10 and 17 weeks of age, provided the best protection. Even at 55 weeks after booster vaccination, chickens were still significantly protected, following severe challenge with either of the three serotypes of Haemophilus paragallinarum. Both bivalent vaccines did not protect against type B challenge. Furthermore the oil-adjuvant vaccines induced higher HI-A titers, which correlate with protection, compared to the A1(OH)3-potentiated vaccine. The results show that type B strains are pathogenic and constitute a distinct immunotype and thus a Coryza vaccine should contain three serotypes to obtain a broader protection against all serotypes.