Association between clinical and salivary microbial parameters during orthodontic treatment with removable appliances with or without use of fluoride mouth rinse.

AIM: To evaluate the correlation between clinical and salivary microbial parameters during treatment with removable orthodontic appliances with or without use of fluoride mouth rinse. MATERIALS AND METHODS: A group of 48 patients completed this randomized, controlled, parallel-group, clinical pilot study. 24 patients of the test group (TG) rinsed after tooth brushing with a fluoride mouth rinse (100 ppm AmF/150 ppm NaF) while 21 patients of the control group (CG) did not. Clinical parameters [Approximal Plaque Index (API), Papillary Bleeding Index (PBI)] as well as levels of salivary mutans streptococci (MS) and lactobacilli (LB) were assessed at baseline and after 3, 6, 9 and 12 months. Compliance was documented by participants. Appliance wear-times were estimated retrospectively by the patients. All participants received the same brushing instructions and were supplied with the same toothbrush/toothpaste. RESULTS: A significant correlation of API values with MS levels (p=0.0003) or with LB levels (p=0.001) was observed. Furthermore, appliance wear-times were significantly associated with API values (p=0.02). The changes of MS or LB levels between beginning and end of the study did not differ significantly between study groups. The changes of the API scores showed slightly different median values (-3.5 in the TG vs. 0 in the CG), the difference, however, was not significant. CONCLUSIONS: The results emphasise the need for a careful monitoring of the oral hygiene status in patients with removable orthodontic appliances. Larger controlled clinical trials are necessary to investigate treatment options such as use of supplementary fluoride mouth rinse.

Persisting myelin oligodendrocyte glycoprotein antibodies in aquaporin-4 antibody negative pediatric neuromyelitis optica.

BACKGROUND: Recently we showed that antibodies to myelin oligodendrocyte glycoprotein (MOG) can be found in aquaporin-4 (AQP4)-immunoglobulin (IgG) seronegative pediatric and adult patients with definite and high-risk neuromyelitis optica (NMO). OBJECTIVE: The purpose of this study was to describe the clinical characteristics and temporal dynamics of MOG-IgG in AQP4-IgG seronegative pediatric patients presenting with definite NMO. METHODS: Children with definite NMO who were referred for further testing of serum antibodies for AQP4 and MOG with a cell-based assay were included in this study. Clinical disease course, cerebrospinal fluid and magnetic resonance imaging (MRI) studies of these patients were reviewed. RESULTS: Between 2008 and 2012 eight children who fulfilled the diagnostic criteria of definite NMO were recruited. Two children with definite NMO tested positive for AQP4-IgG but were negative for MOG-IgG antibodies. Three children had an absence of AQP4-IgG and MOG-IgG antibodies. Three children with definite NMO had high titers of serum MOG-IgG antibodies (≥1: 160), but no AQP4-directed humoral immune response. Longitudinal analysis of serum samples of the latter three children showed persisting high MOG-IgG titers over time. CONCLUSION: Pediatric patients presenting with clinical symptoms and MRI findings highly suggestive of NMO but with high and persisting MOG-IgG antibody titers are most likely to represent a distinct subgroup of acute demyelinating diseases with important clinical and therapeutic implications.

Autoantibody status, neuroradiological and clinical findings in children with acute cerebellitis.

BACKGROUND: Acute cerebellitis (AC) in children and adolescents is an inflammatory disease of the cerebellum due to viral or bacterial infections but also autoimmune-mediated processes. OBJECTIVE: To investigate the frequency of autoantibodies in serum and CSF as well as the neuroradiological features in children with AC. MATERIAL AND METHODS: Children presenting with symptoms suggestive of AC defined as acute/subacute onset of cerebellar symptoms and MRI evidence of cerebellar inflammation or additional CSF pleocytosis, positive oligoclonal bands (OCBs), and/or presence of autoantibodies in case of negative cerebellar MRI. Children fulfilling the above-mentioned criteria and a complete data set including clinical presentation, CSF studies, testing for neuronal/cerebellar and MOG antibodies as well as MRI scans performed at disease onset were eligible for this retrospective multicenter study. RESULTS: 36 patients fulfilled the inclusion criteria for AC (f:m = 14:22, median age 5.5 years). Ataxia was the most common cerebellar symptom present in 30/36 (83 %) in addition to dysmetria (15/36) or dysarthria (13/36). A substantial number of children (21/36) also had signs of encephalitis such as somnolence or seizures. In 10/36 (28 %) children the following autoantibodies (abs) were found: MOG-abs (n = 5) in serum, GFAPα-abs (n = 1) in CSF, GlyR-abs (n = 1) in CSF, mGluR1-abs (n = 1) in CSF and serum. In two further children, antibodies were detected only in serum (GlyR-abs, n = 1; GFAPα-abs, n = 1). MRI signal alterations in cerebellum were found in 30/36 children (83 %). Additional supra- and/or infratentorial lesions were present in 12/36 children, including all five children with MOG-abs. Outcome after a median follow-up of 3 months (range: 1 a 75) was favorable with an mRS ≤2 in 24/36 (67 %) after therapy. Antibody (ab)-positive children were significantly more likely to have a better outcome than ab-negative children (p = .022). CONCLUSION: In nearly 30 % of children in our study with AC, a range of abs was found, underscoring that autoantibody testing in serum and CSF should be included in the work-up of a child with suspected AC. The detection of MOG-abs in AC does expand the MOGAD spectrum.

A novel ex vivo set-up for dynamic long-term characterization of processes on mucosal interfaces by confocal imaging and simultaneous cytokine measurements.

We present a novel organ-explant imaging system for easy and cost-effective extended-time observation of host-pathogen interactions at mucosal interfaces. Data are complemented by parallel cytokine measurements at high temporal resolution. The set-up is based on a custom-built reusable organ chamber compatible with standard microscopes. Luminal and basal side of the explanted mucosa are connected to separate channels for optimized incubation and cytokine measurements, oxygen is provided via membrane oxygenation. Dynamic imaging with confocal microscopy permits a detailed analysis of the dynamics of pathogen-host cell interactions at the mucosal interface and the neighbouring tissue at high resolution. The system can be applied to various hollow organs with few modifications. Here we present first applications to study representative infections such as uropathogenic Escherichia coli (UPEC) infections in the urinary bladder or amoebiasis of the colon by using mouse organs. We show (i) intracellular bacteria in UPEC infections, (ii) phagocytic events on tissue during infection, as well as (iii) tissue invasion of virulent protozoans into epithelia. The versatility of this system and its higher degree of control in comparison with both traditional explant microscopy and in vivo two photon imaging solutions make it a valuable and easy-to-use addition to other current imaging techniques.

Bone remodeling around stable uncemented titanium stems during the second decade after total hip arthroplasty: a DXA study at 12 and 17 years.

UNLABELLED: In a cohort study, bone mineral density (BMD) around uncemented femoral components after total hip arthroplasty (THA) was evaluated. The results suggest that there are no clinically relevant changes in overall periprosthetic BMD in the second decade. However, continuous remodeling with limited proximal bone loss (stress-shielding) occurs, predominantly in female patients. INTRODUCTION: Progressive periprosthetic bone loss and stress-shielding are a major concern in THA. Little is known about the extent and pattern of periprosthetic bone remodeling around uncemented stems in the second decade. METHODS: In a cohort study, periprosthetic BMD was measured in 131 patients with 146 uncemented CLS stems using dual-energy X-ray absorptiometry (DXA) at a mean of 12 years postoperatively (t1). Patients were followed clinically and radiographically, and a second DXA was performed at a mean of 17 years postoperatively (t2) using the identical protocol. RESULTS: We obtained a complete set of two consecutive DXA measurements for 88 hips (78 patients, 35 male, 43 female). On radiographic evaluation at t1 and t2, regular bone ongrowth was present in all cases and no signs of radiographic loosening, severe bone loss or diaphyseal cortical hypertrophy were detected. There was no clinically relevant change in overall periprosthetic BMD (netavg) between t1 and t2 for both male and female patients. We analyzed the differences in BMD in the periprosthetic regions of interest (ROIs) according to Gruen and found a slight decrease in periprosthetic BMD in ROI 7 in male patients and in ROIs 1, 4, 6 and 7 in female patients. CONCLUSIONS: The study suggests that there are no clinically relevant changes in overall periprosthetic BMD around stable, straight uncemented stems between 12 and 17 years postoperatively. However, continuous remodeling with limited proximal bone loss occurs, predominantly in female patients. After secondary osteointegration of this implant, stress-shielding remains minimal in the second decade.

Aromatic L-amino acid decarboxylase deficiency: clinical features, drug therapy and follow-up.

BACKGROUND: Aromatic L-amino acid decarboxylase (AADC) deficiency is a disorder of biogenic amine metabolism resulting in generalized combined deficiency of serotonin, dopamine and catecholamines. Main clinical features are developmental delay, muscular hypotonia, dystonia, oculogyric crises and additional extraneurological symptoms. Response to therapy has been variable and unsatisfactory; the overall prognosis is guarded. METHODS: To gain more insight into this rare disorder we collected clinical and laboratory data of nine German patients. All patients were clinically examined by one investigator, and their responses to different drug regimes were evaluated by the patients' charts. RESULTS: Symptoms were obvious from early infancy. Later, main neurological features were truncal muscular hypotonia, hypokinesia, oculogyric crises and rigor. Three patients had single seizures. All patients presented distinct extraneurological symptoms, such as hypersalivation, hyperhidrosis, nasal congestion, sleep disturbances and hypoglycaemia. In CSF all patients revealed the pattern typical of AADC with decreased concentrations of homovanillic and 5-hydroxyindoleacetic acid and elevated concentration of 3-ortho-methyldopa. Diagnosis was confirmed by measurement of AADC activity in plasma in all patients. Drug regimes consisted of vitamin B6, dopamine agonists, MAO inhibitors and anticholinergics in different combinations. No patient achieved a complete recovery from neurological symptoms, but partial improvement of mobility and mood could be achieved in some. CONCLUSION: AADC deficiency is a severe neurometabolic disorder, characterized by muscular hypotonia, dystonia, oculogyric crises and additional extraneurological symptoms. Medical treatment is challenging, but a systematic trial of the different drugs is worthwhile.

Socio-medicinal aspects of vibration-induced white finger disease.

PURPOSE: The influence of vibration-induced white finger disease on the quality of life and possible social consequences is the subject of the study presented herein. METHOD: The data acquisition was carried out by means of a standardized questionnaire. Parameters such as quality of life, professional practice, prevention and social security were assessed among other things. RESULTS: Nearly three quarters of the interviewees (n = 115) did not consult a physician with the occurrence of the first complaints. Physicians frequently made the correct diagnosis only with delay. From the first occurrence of symptoms to the acknowledgment as an occupational disease 0.5-34.5 years had usually elapsed. The quality of life affected the patients and their families. Change of profession and unemployment were frequently associated with substantial problems. There is clear need for information regarding the clinical picture, protective possibilities in the workplace, recognition as an occupational disease and financial problems. The introduction of industrial safety measures was not substantially affected by the occurrence of the disease. CONCLUSIONS: A quick diagnosis and the recognition of this occupational disease are important in view of its potential reversibility upon discontinuation of the exposition to vibration. As a consequence, intensified preventive measures need to be called for.

Reliability of three different visual acuity testing procedures in school children.

AIM: To evaluate the usability and reliability of three different visual acuity (VA) testing procedures using Landolt C's in 8 positions with a semi-automated computer program in school children. METHODS: 100 school children (median 7 years, 59 boys and 41 girls) were included; only the better eye was tested. We used the semi-automated computer program CORVIS.VT in a forced choice method. Three different test strategies were employed, each two times: A) DIN, B) Standard-Staircase and C) Best-PEST procedure with sequences A, B, C or A, C, B. RESULTS: Average testing time was 100 s +/- 45 (DIN), 59 s +/- 36 (Staircase) and 77 s +/- 25 (Best-PEST). The mean VA estimated with DIN was equivalent to that with the Best-PEST procedure. However, the mean VA with Standard-Staircase was one line less. In DIN, 76% of the retest scores were within 0.1 logMAR unit of the initial test score (Staircase: 72%, Best-PEST 73%). The 95% confidence interval of test-retest reliability was calculated to be -0.05 +/- 0.24 logMAR in DIN, +0.02 +/- 0.32 logMAR in Staircase, and 0.00 +/- 0.29 logMAR in Best-PEST. CONCLUSION: A high percentage of children aged 6 to 9 years (98%) can be tested with Landolt C's (8 positions). We found a decreasing test-retest reliability starting from DIN via Best-PEST to Staircase in this configuration.

Cyclic-alternating versus response-oriented chemotherapy in small-cell lung cancer: a German multicenter randomized trial of 321 patients.

To test whether alternating chemotherapy is a favorable treatment modality in small-cell lung cancer (SCLC), 334 patients were randomized to receive either fixed cyclic-alternating treatment with ifosfamide/etoposide (IE), cyclophosphamide, doxorubicin, and vincristine (CAV), or response-oriented treatment with IE therapy up to maximal response and subsequently an immediate switch to CAV. In both arms, six cycles were given in 3-week intervals. After chemotherapy, patients with limited-stage disease received chest irradiation with 45 Gy. Prophylactic cranial irradiation with 30 Gy was applied to all complete responders. No maintenance therapy was given to patients with complete response. Minimum follow-up was 2 years. Of 321 assessable patients, the overall response rate was 70% for cyclic alternating and 77% for response-oriented treatment. Complete remission (CR) rates were 26% versus 26%. The median survival times were 9.7 months for cyclic-alternating versus 10.7 months for response-oriented treatment; the 2-year survival rates were 11% versus 9%. In limited-stage disease (LD) patients, there was a median survival of 12.5 months versus 12.3 months and a 2-year survival rate of 21% versus 18%. In extensive-stage disease (ED) patients, median survival was 8.5 versus 9.1 months, and the 2-year survival rate 3% versus 4%. From these results, we conclude that the cyclic-alternating treatment according to the hypothesis of Goldie et al has no advantage in comparison to a sequential treatment strategy with an immediate switch to a second-line protocol at the time no further response to first-line therapy is seen. Our major aim in the treatment of SCLC is to administer an active regimen at any time during the course of treatment regardless of whether sequential or alternating therapy is used.

Results of interleukin-2-based treatment in advanced melanoma: a case record-based analysis of 631 patients.

PURPOSE: In patients with stage IV melanoma, durable responses have been reported with treatment regimens that involve high-dose interleukin-2 (IL-2). We analyze long-term results of 631 melanoma patients from 12 institutions who had received IL-2 alone, in combination with interferon alfa 2a or 2b (IFNalpha), or with cytotoxic drugs. METHODS: Case records that contained pretreatment parameters, response data, and updated survival information were collected. After univariate analysis, the multivariate evaluation of the impact of pretreatment parameters on response and survival was performed by logistic regression and Cox's regression, respectively. RESULTS: Patients were divided into four groups according to treatment: IL-2 alone (n=117), IL-2 and chemotherapy (n=49), IL-2 and IFNalpha (n=153), and IL-2, chemotherapy, and IFNalpha (n=312). The median survival of all patients was 10.5 months and the 2- and 5-year survival rates were 19.9% and 10.4%, respectively. Independent prognostic factors for response and survival were entirely different, treatment group being the only significant factor for response, and serum lactate dehydrogenase (LDH), metastatic site, and performance predicting survival. The addition of IFNalpha to IL-2 was associated with prolonged survival, but the effect of additional chemotherapy was less obvious. CONCLUSION: Serum LDH, metastatic site, and performance status are useful stratification factors for randomized trials in metastatic melanoma. The improved long-term survival rates observed in melanoma patients treated with IL-2/IFNalpha-containing regimens are notable in contrast to the reported 5-year survival rates of 2% to 6% achieved with chemotherapy, but because selection bias cannot be ruled out, the impact of IL-2, as well as all other components of the treatment regimens, on survival needs to be confirmed in prospective randomized trials.

Extracellular matrix proteins and matrix metalloproteinases differ between various right and left ventricular sites in end-stage cardiomyopathies.

This study was undertaken to investigate whether there might be differences in the distribution of extracellular matrix (ECM) proteins and matrix metalloproteinases (MMPs), depending on their specific sites within the heart. We investigated 33 explanted human hearts, 15 with dilated cardiomyopathy (DCM) and 18 with ischemic cardiomyopathy (ICM). Transmural samples from the right ventricle, the interventricular septum and the left ventricle, either from near the apex or from near the base were taken from every heart. Frozen sections were processed for connective tissue staining and immunohistochemistry for collagens type I, III, IV, laminin and fibronectin, as well as MMP-1, -2 and -9. Volume densities of laminin in ICM as well as of fibronectin and collagen types I and IV in DCM showed significant differences between right and left ventricular sites. The volume densities of matrix proteins usually did not reveal significant differences among the three left ventricular sites tested in both DCM and ICM. MMPs partly showed differences between the right and the left ventricular myocardium. These results suggest that the distributions of ECM proteins and MMPs differ between the two ventricles in both end-stage DCM and ICM. This gives rise to the hypothesis that a specific pattern of ECM degradation exists in the right and left ventricular myocardium.

Modelling the natural history of geographic atrophy in patients with age-related macular degeneration.

PURPOSE: To model the natural course of geographic atrophy (GA) in patients with age-related macular degeneration (AMD). METHODS: Data on the natural course of GA were collected in the multi-center, longitudinal, prospective observational FAM study. The size of GA was measured by autofluorescence scanning laser ophthalmoscopy. The natural course of GA is modelled by two different mixed effect models (MEM). Both models are compared with respect to the correctness of the model assumptions, goodness of fit, and predictive behavior. RESULTS: The linear model results in better prediction, the non-linear model is more in agreement with the model assumptions. The non-linear model fits the data for small and large areas of GA better, while the linear model seems to be more adequate for the medial areas. More data will be needed to study the interplay of both models in more detail. CONCLUSIONS: The natural course of GA varies extremely between individuals. However, reliable factors for the explanation of this variability have so far not been established. MEM are useful for describing "inter-individual" as well as "intra-individual" influences without the need for precise knowledge of the influencing factors. Using MEM to evaluate data on the natural history of GA allows one to derive parameter estimates, which could be used to design interventional trials for modes of therapy with a potential to reduce or stop the progression of GA in patients with AMD.

Villonodular synovitis of the shoulder in the elderly.

Villonodular synovitis of the shoulder developed in two elderly patients. Huge soft tissue mass, marked joint effusion, and radiographs demonstrating severe osteoarthritic changes characterized these patients. Localized shoulder muscle atrophy accounts for residual painfree limitation of active shoulder motion following synovectomy of the shoulder joint.

Prognostic factors for response and survival in patients with metastatic melanoma receiving immunotherapy.

Sixty-five patients with advanced melanoma treated in phase II trials with interferon-alpha and high dose interleukin-2 were analysed for pretreatment prognostic parameters. Three levels of response were used: objective remission [three complete response (CR)/14 partial response (PR)], stable disease and progression. Elevated lactate dehydrogenase (LDH), impaired performance status and high tumor load were associated with poor response. Multivariate analysis considering two levels of response [CR/PR vs stable disease (SD)/progressive disease (PD)] did not reveal any model with more than one significant factor. Considering survival, LDH was also a strong factor. Additional prognostic factors here were performance status, metastatic sites, alkaline phosphatase and tumor load. A Cox regression analysis revealed LDH, performance status and metastatic sites as independent factors. The prognostic values of these parameters will have to be confirmed in a larger patient cohort. Using the landmark method, it was estimated whether the response obtained after two cycles of treatment predicted survival. Patients with PD at this time had a median further survival of 6 months, SD of 27 months, and PR/CR of more than 31 months. This observation may help making decisions at this time.

Arthroscopic treatment of osteochondral lesions of the talus.

In a study of twenty-four patients (twenty-four ankles) with a symptomatic osteochondral lesion of the talus, eighteen of the lesions were found to be associated with trauma. The lesions were evaluated both radiographically and by arthroscopy. The method of treatment was determined at arthroscopy by observing the nature of the articular cartilage overlying the lesion. The cartilage was graded from I to III based on its appearance. It was found that a lesion can progress from grade I to grade III while under observation. There was a lack of correlation between the radiographic appearance and the findings at arthroscopy. The results after an average length of follow-up of thirty months (range, twenty to forty-four months) indicated that osteochondral lesions over which the cartilage is intact (grade I) are best treated by simple restriction of sports activities. Lesions in which the overlying cartilage is soft (grade II) can be treated through the arthroscope by drilling and those in which the overlying cartilage is frayed (grade III) can be treated through the arthroscope by curettage, with minimum morbidity and good results.

Manipulation and external fixation of metacarpal fractures.

We have developed a method of manipulation and external fixation of metacarpal fractures using Kirschner wires bonded with acrylic resin. This simple procedure requires no special instruments and it facilitates accurate reduction and stable fixation of the fracture while allowing free movement of the hand. Access to the wound is unhampered in open fractures. Thirty-six fractures were treated by this technique. All healed within five weeks, during which time free movement of the hand was encouraged. There were no complications.

In vitro performance of intramedullary cement restrictors in total hip arthroplasty.

Contemporary cementing techniques in total hip arthroplasty include the use of a cement restrictor to occlude the intramedullary canal. As there are many different designs currently available it was the aim of our study to compare the stability of eight different systems. We investigated the displacement and the ability to occlude the femur of these cement restrictors during standardised cementing of artificial and fresh frozen femora. The maximal intramedullary pressures and the displacement of the plugs were continuously recorded and statistically evaluated. The results revealed significant differences between the tested cement restrictors. The expandable REX Cement Stop and the Exeter Plug achieved the highest stability and the least cement leakage. The more rigid designs (Palacos Plug, BUCK, Universal) in contrast showed inferior performance. Our biomechanical study emphasises the importance of cement restrictor selection, which can have a crucial influence on the fixation of a cemented total hip replacement.

Cystic change in the wrist, causing carpal tunnel syndrome.

An unusual case of a degenerative cyst, causing median nerve compression within the carpal tunnel, is reported.

The reproducibility of the ratio of volume flow in the common femoral vein and artery for quantification of the severity of venous insufficiency.

BACKGROUND: The ratio of volume flow in the common femoral vein and artery denoted as venous-arterial Flowindex (VAFI) is significantly increased in venous insufficiency according the clinical grade of the disease. This study was done to investigate the reliability and reproducibility of VAFI as quantitative pattern. PATIENTS AND METHODS: In 43 patients with varicose veins C4-6 EPAS,D,PPR (PVV), 40 with postthrombotic syndrome C4-6 ESAS,D,PPR,O (PTS) and 48 healthy volunteers volume flow in the common femoral vein (VFV) and artery (VFA) were measured by duplex. Division of VFV by VFA calculated VAFI. VAFI-measurement was repeated 5 times at an interval of ten minutes in 63 subjects (23 PVV, 20 PTS, 20 healthy) and it was performed at three different days in 68 subjects (20 PVV, 20 PTS, 28 healthy). RESULTS: Mean VAFI +/- standard deviation was 1.39 +/- 0.26 in PVV, 1.42 +/- 0.26 in PTS and 0.93 +/- 0.13 in healthy veins (p < 0.001). VAFI remained stable and significantly increased (p < 0.001) in PVV and PTS compared to healthy veins during 40 minutes and also within three different days. CONCLUSION: The venous-arterial flowindex VAFI is a reproducible pattern of the hemodynamic severity in venous insufficiency.