Evaluation of colour vision impairment during acute hypobaric hypoxia in aviation medicine: a randomized controlled trial.

The digitization of aircraft cockpits places high demands on the colour vision of pilots. The present study investigates colour vision changes upon acute exposure to hypobaric hypoxia. The digital Waggoner Computerized Color Vision Test and the Waggoner D-15 were performed by 54 healthy volunteers in a decompression chamber. Respective altitude levels were sea level, 10,000 or 15,000 ft for exposure periods of 15 and 60 min, respectively. As for 60 min of exposure a significant decrease in colour perception was found between subjects at 15,000 ft as compared to the control group as well as between subjects at 15,000 ft as compared to subjects at 10,000 ft. No significant difference was found in the comparison within the 15,000 ft groups across time points pre-, peri-, and post-exposure. Thus, pilots appear to experience only minor colour vision impairment up to an exposure altitude of 15,000 ft over 60 min of exposure.

R0 resection following chemo (radio)therapy improves survival of primary inoperable pancreatic cancer patients. Interim results of the German randomized CONKO-007± trial.

PURPOSE: Chemotherapy with or without radiotherapy is the standard in patients with initially nonmetastatic unresectable pancreatic cancer. Additional surgery is in discussion. The CONKO-007 multicenter randomized trial examines the value of radiotherapy. Our interim analysis showed a significant effect of surgery, which may be relevant to clinical practice. METHODS: One hundred eighty patients received induction chemotherapy (gemcitabine or FOLFIRINOX). Patients without tumor progression were randomized to either chemotherapy alone or to concurrent chemoradiotherapy. At the end of therapy, a panel of five independent pancreatic surgeons judged the resectability of the tumor. RESULTS: Following induction chemotherapy, 126/180 patients (70.0%) were randomized to further treatment. Following study treatment, 36/126 patients (28.5%) underwent surgery; (R0: 25/126 [19.8%]; R1/R2/Rx [n = 11/126; 6.1%]). Disease-free survival (DFS) and overall survival (OS) were significantly better for patients with R0 resected tumors (median DFS and OS: 16.6 months and 26.5 months, respectively) than for nonoperated patients (median DFS and OS: 11.9 months and 16.5 months, respectively; p = 0.003). In the 25 patients with R0 resected tumors before treatment, only 6/113 (5.3%) of the recommendations of the panel surgeons recommended R0 resectability, compared with 17/48 (35.4%) after treatment (p < 0.001). CONCLUSION: Tumor resectability of pancreatic cancer staged as unresectable at primary diagnosis should be reassessed after neoadjuvant treatment. The patient should undergo surgery if a resectability is reached, as this significantly improves their prognosis.

Use of CAD-based pre-bent implants reduces theatre time in orbital floor reconstruction: results of a prospective study.

In this prospective study we evaluated the duration of insertion and the accuracy of fitting of computer-aided design (CAD)-based pre-bent orbital floor plates compared with non-preformed orbital plates in reconstruction of the orbital floor. Thirty-six patients with unilateral fractures of the orbital floor were included; pre-bent plates were used in 25 and non-preformed plates in 11. Preoperative computed tomography (CT) scans were used for CAD of individualised implants. The anatomy of the affected orbit was virtually reconstructed "slice by slice". Individually pre-bent plates were generated using a stereolithographic model of the reconstructed orbit. The mean (SD) duration of insertion was significantly reduced when pre-bent orbital plates were used (5.5 (5.4) min) compared with non-preformed meshes (11.1 (7.7) min). The congruence of pre-bent plates to the infraorbital rim did not differ from that of non-preformed plates. The accuracy of fit was rated as "accurate" in 24 cases. CAD-based individualised titanium meshes reduce theatre time compared with non-preformed orbital plates. Our results confirm the efficacy of CAD-based pre-bent plates in reconstruction of the orbital floor.

Survival benefit for patients treated in a certified head and neck tumor center.

OBJECTIVE: Increasing effort has been put in the implementation and certification of head and neck tumor centers in order to establish standardized, quality assured health care for head and neck tumor patients. This study evaluated survival rates after treatment in a certified head and neck tumor center (CHNTC) vs. a non-certified head and neck tumor center (non-CHNTC) in Middle Franconia, Germany. PATIENTS AND METHODS: Age, sex, possible obituary, and typical relevant prognostic variables were analyzed. Diagnosis was recorded according to ICD10. Clinical and pathological TNM staging, tumor grading, localization, R-stage, and morphology were assessed (ICD-0). Patients diagnosed with oral cancer (N=1047) were divided into groups based on where they received their primary treatment; CHNTCs or non-CHNTCs. RESULTS: Patients treated at CHNTCs had significantly higher survival rates vs. those treated at non-CHNTC (p=0.023) in univariate analysis. In a Cox regression model, survival rates for patients with pN0 and pN+ stage were similar at both types of centers. Men with pN0 had significantly lower survival rates (HR=0.497, p<0.001). Age had a statistically significant influence on survival rates independently from pN stage (HR=1.031 per year, p<0.001 in both groups). CONCLUSIONS: Patients treated at CHNTC had better survival rates than those treated at non-CHNTC.

Bruch's membrane opening-based optical coherence tomography of the optic nerve head: a useful diagnostic tool to detect glaucoma in macrodiscs.

PurposeTo compare Bruch's membrane opening (BMO)-based spectral domain optical coherence tomography (SD-OCT) and margin based confocal scanning laser tomography (CSLT) of the optic nerve head (ONH) to visual field function in large optic discs (macrodiscs) and to assess performance for glaucoma detection.MethodsIn a case-control, cross-sectional study, 125 eyes of 125 patients with disc size >2.45 mm2, thereof 44 glaucoma and 11 ocular hypertension (OHT) patients and 70 healthy controls underwent SD-OCT and CSLT examination, visual field testing and clinical evaluation. Mean outcome measures BMO-based minimum rim width (BMO-MRW), retinal nerve fiber layer thickness (RNFLT) in SD-OCT, and rim area measured in CSLT were compared and correlated to visual field function.ResultsAll participants had a mean disc area of 2.91±0.38 mm2 in CSLT and a BMO area of 2.45±0.39 mm2 (r=0.76;P<0.001). In glaucoma patients, visual field mean deviation was -10.0±6.1 dB. Global BMO-MRW correlated better to visual field function (Spearman's Rho (ρ)=0.71; P<0.001) than RNFLT (ρ=0.52;P<0.001) and CSLT rim area (ρ=0.63; P<0.001). BMO-MRW was significantly decreased with higher visual field loss (P<0.001). In ROC analysis, diagnostic power to differentiate glaucoma patients and healthy controls was highest for BMO-MRW (Area under curve, AUC=0.96; sensitivity at 95% specificity=82%). Rim area in CSLT (AUC=0.91; sensitivity=61.0%; P=0.04) and RNFLT (AUC=0.89; sensitivity=61%; P=0.01) were significantly less powerful.ConclusionsIn macrodiscs, BMO-MRW has the best diagnostic power to discriminate glaucoma patients from normal controls compared to RNFLT and rim area in CSLT. Additionally, BMO-MRW seems to reflect the structure-function relationship better than the other two parameters.

Gingival esthetics and oral health-related quality of life in patients with cleft lip and palate.

While the oral health-related quality of life (OHRQoL) is known to be reduced in patients with cleft lip and palate (CLP), its inter-dependency with the soft tissue characteristics of the CLP area remains unclear. This study aimed to evaluate the soft tissue characteristics in the treated cleft area in order to investigate whether gingival esthetics correlate with OHRQoL. Thirty-six patients with unilateral or bilateral CLP (46 cleft areas) were investigated after secondary/tertiary alveolar bone grafting and orthodontic/prosthetic implant treatment using an adapted score to rate gingival esthetics (clinical esthetic score, CES). The patient's OHRQoL was determined using the German short version of the Oral Health Impact Profile questionnaire (OHIP-G14). The results showed a significantly better rating in patients with their own teeth in situ (12.05±1.10) than in patients with implants (6.95±4.78) or prosthetics (4.00±3.58). The best OHRQoL values were achieved by patients with their own teeth integrated into the cleft area (1.32±2.31), followed by patients with implants (2.33±2.33) and prosthetics (3.75±5.87). A significant (P=0.017) correlation was found between OHIP-G14 and CES scores, suggesting an increased OHRQoL in cases with higher oral esthetics in the cleft area. The therapeutic strategy contributes to both gingival esthetics and OHRQoL. The patient's subjective perception of OHRQoL can be attributed to objective gingival esthetic ratings.

Spectral-domain optical coherence tomography findings of the macula in 500 consecutive patients with uveitis.

PurposeTo analyze the macular structure in a large series of consecutive patients with different types of uveitis using spectral-domain optical coherence tomography (SD-OCT).Patients and methodsFive hundred eyes of 500 consecutive patients with anterior, intermediate, posterior, and panuveitis underwent standardized macular examination using SD-OCT. Central retinal thickness (CRT), macular volume (MV), and presence of cystoid macular edema (CME), diffuse macular edema (DME), serous retinal detachment (SRD), epiretinal membrane with (ERM+) and without (ERM-) retinal surface wrinkling were determined.ResultsThe anatomic location of inflammation affected significantly CRT and MV (P<0.001, respectively), with the highest values in intermediate and panuveitis. CME was seen in 25% of all uveitic eyes, DME in 11%, SRD in 8%, ERM+ in 18%, and ERM- in 13%. CME was most frequent in intermediate (40%) and panuveitis (36%); DME was most frequent in panuveitis (18%) and posterior uveitis (17%); SRD was most frequent in panuveitis (15%) and posterior uveitis (10%); ERM+ was most frequent in panuveitis (45%) and intermediate uveitis (30%); and ERM- was most frequent in intermediate (14%) and posterior uveitis (15%).ConclusionSD-OCT of the macula is recommended for all uveitis patients. CRT, MV, and the incidence of CME were highest in intermediate and panuveitis.

Embryonic disruption of the candidate dyslexia susceptibility gene homolog Kiaa0319-like results in neuronal migration disorders.

Developmental dyslexia, the most common childhood learning disorder, is highly heritable, and recent studies have identified KIAA0319-Like (KIAA0319L) as a candidate dyslexia susceptibility gene at the 1p36-34 (DYX8) locus. In this experiment, we investigated the anatomical effects of knocking down this gene during rat corticogenesis. Cortical progenitor cells were transfected using in utero electroporation on embryonic day (E) 15.5 with plasmids encoding either: (1) Kiaa0319l small hairpin RNA (shRNA), (2) an expression construct for human KIAA0319L, (3) Kiaa0319l shRNA+KIAA0319L expression construct (rescue), or (4) controls (scrambled Kiaa0319l shRNA or empty expression vector). Mothers were injected with 5-bromo-2-deoxyuridine (BrdU) at either E13.5, E15.5, or E17.5. Disruption of Kiaa0319l function (by knockdown, overexpression, or rescue) resulted in the formation of large nodular periventricular heterotopia in approximately 25% of the rats, which can be seen as early as postnatal day 1. Only a small subset of heterotopic neurons had been transfected, indicating non-cell autonomous effects of the transfection. Most heterotopic neurons were generated in mid- to late-gestation, and laminar markers suggest that they were destined for upper cortical laminae. Finally, we found that transfected neurons in the cerebral cortex were located in their expected laminae. These results indicate that KIAA0319L is the fourth of four candidate dyslexia susceptibility genes that is involved in neuronal migration, which supports the association of abnormal neuronal migration with developmental dyslexia.

Factors influencing relative speech intelligibility in patients with oral squamous cell carcinoma: a prospective study using automatic, computer-based speech analysis.

Oral squamous cell carcinoma (OSCC) and its treatment impair speech intelligibility by alteration of the vocal tract. The aim of this study was to identify the factors of oral cancer treatment that influence speech intelligibility by means of an automatic, standardized speech-recognition system. The study group comprised 71 patients (mean age 59.89, range 35-82 years) with OSCC ranging from stage T1 to T4 (TNM staging). Tumours were located on the tongue (n=23), lower alveolar crest (n=27), and floor of the mouth (n=21). Reconstruction was conducted through local tissue plasty or microvascular transplants. Adjuvant radiotherapy was performed in 49 patients. Speech intelligibility was evaluated before, and at 3, 6, and 12 months after tumour resection, and compared to that of a healthy control group (n=40). Postoperatively, significant influences on speech intelligibility were tumour localization (P=0.010) and resection volume (P=0.019). Additionally, adjuvant radiotherapy (P=0.049) influenced intelligibility at 3 months after surgery. At 6 months after surgery, influences were resection volume (P=0.028) and adjuvant radiotherapy (P=0.034). The influence of tumour localization (P=0.001) and adjuvant radiotherapy (P=0.022) persisted after 12 months. Tumour localization, resection volume, and radiotherapy are crucial factors for speech intelligibility. Radiotherapy significantly impaired word recognition rate (WR) values with a progression of the impairment for up to 12 months after surgery.

Medial orbital wall reconstruction with flexible Ethisorb patches.

OBJECTIVES: The aim of this study was to analyse the long-term result after reconstruction of the medial orbital wall with a flexible, biodegradable material (Ethisorb). MATERIALS AND METHODS: During a period of almost 8 years, 31 patients with a medial orbital wall fracture were analysed retrospectively. Inclusion criteria were patients with a maximum size fracture of the orbital medial wall measuring 1.5-2 cm(2). Exophthalmos, enophthalmos, bulbus motility, diplopia and skin sensation were investigated over a period of 6 months. In all patients, the medial orbital wall was reconstructed with Ethisorb patches. RESULTS: No significant intraoperative complications were detected. No postoperative infection, abscess or seroma was found in any of the patients receiving an Ethisorb patch. CONCLUSIONS: The advantage of the semiflexibility of the Ethisorb patch is that it supplies an anatomically correct fit to the orbital medial wall but does not require fixation by screws or the use of sutures. CLINICAL RELEVANCE: The low rate of reported bulbus motility disturbance, diplopia, exophthalmos and enophthalmos demonstrates acceptable results after medial orbital wall reconstruction using the Ethisorb patch.

Frequency doubling technique perimetry and spectral domain optical coherence tomography in patients with early glaucoma.

PURPOSE: To assess the combined diagnostic power of frequency-doubling technique (FDT)-perimetry and retinal nerve fibre layer (RNFL) thickness measurements with spectral domain optical coherence tomography (SDOCT). METHODS: The study included 330 experienced participants in five age-related groups: 77 'preperimetric' open-angle glaucoma (OAG) patients, 52 'early' OAG, 50 'moderate' OAG, 54 ocular hypertensive patients, and 97 healthy subjects. For glaucoma assessment in all subjects conventional perimetry, evaluation of fundus photographs, FDT-perimetry and RNFL thickness measurement with SDOCT was done. Glaucomatous visual field defects were classified using the Glaucoma Staging System. FDT evaluation used a published method with casewise calculation of an 'FDT-score', including all missed localized probability levels. SDOCT evaluation used mean RNFL thickness and a new individual SDOCT-score considering normal confidence limits in 32 sectors of a peripapillary circular scan. To examine the joined value of both methods a combined score was introduced. Significance of the difference between Receiver-operating-characteristic (ROC) curves was calculated for a specificity of 96%. RESULTS: Sensitivity in the preperimetric glaucoma group was 44% for SDOCT-score, 25% for FDT-score, and 44% for combined score, in the early glaucoma group 83, 81, and 89%, respectively, and in the moderate glaucoma group 94, 94, and 98%, respectively, all at a specificity of 96%. ROC performance of the newly developed combined score is significantly above single ROC curves of FDT-score in preperimetric and early OAG and above RNFL thickness in moderate OAG. CONCLUSION: Combination of function and morphology by using the FDT-score and the SDOCT-score performs equal or even better than each single method alone.

[Prevalence of glaucomatous optic nerve atrophy among a working population in Germany diagnosed by a telemedical approach]. / Telemedizinische Erfassung der Prävalenz der glaukomatösen Optikusatrophie in einer arbeitenden Bevölkerungsgruppe.

PURPOSE: The aim of this study was to determine the prevalence of glaucomatous optic nerve atrophy among a working population in Germany by secondary evaluation of a study conducted to estimate the prevalence of retinal microangiopathic abnormalities by telemedical examination of the retina. PATIENTS AND METHODS: From August 2002 until January 2004 the retina and optic nerve head were examined in 19,294 Caucasians using a non-mydriatic fundus camera (Kowa, nonmyd-alpha 45), which produces colour images with 45 degrees. The images of the retina and optic nerve head were evaluated telemedically by glaucoma specialists in respect to optic nerve pathologies and microangiopathic abnormalities by a standardised procedure. Glaucomatous optic nerve atrophy was diagnosed when specific glaucomatous morphological alterations of the optic nerve head were present. A complete medical history including reported elevated intraocular pressure (IOP) and blood pressure was obtained. RESULTS: The intra-observer and inter-observer reliability were 0.884 and 0.740, respectively. Cronbach's alpha for two evaluation cycles each of two observers was 0.870. The prevalences of glaucomatous optic nerve atrophy in the different age groups were 0.07 % (45 - 49 years), 0.40 % (50 - 54 years), 0.45 % (55 - 59 years) and 0.82 % (60 - 64 years). Age could be established as an important risk factor for glaucomatous optic nerve atrophy, while no influence of gender or family history was found. CONCLUSION: Telemedical evaluation of colour images of the retina and optic nerve acquired by a non-mydriatic fundus camera allows a fast and efficient screening of many subjects with medium reliability.

Comparison of classifiers applied to confocal scanning laser ophthalmoscopy data.

OBJECTIVES: Comparison of classification methods using data of one clinical study. The tuning of hyperparameters is assessed as part of the methods by nested-loop cross-validation. METHODS: We assess the ability of 18 statistical and machine learning classifiers to detect glaucoma. The training data set is one case-control study consisting of confocal scanning laser ophthalmoscopy measurement values from 98 glaucoma patients and 98 healthy controls. We compare bootstrap estimates of the classification error by the Wilcoxon signed rank test and box-plots of a bootstrap distribution of the estimate. RESULTS: The comparison of out-of-bag bootstrap estimators of classification errors is assessed by Spearman's rank correlation, Wilcoxon signed rank tests and box-plots of a bootstrap distribution of the estimate. The classification methods random forests 15.4%, support vector machines 15.9%, bundling 16.3% to 17.8%, and penalized discriminant analysis 16.8% show the best results. CONCLUSIONS: Using nested-loop cross-validation we account for the tuning of hyperparameters and demonstrate the assessment of different classifiers. We recommend a block design of the bootstrap simulation to allow a statistical assessment of the bootstrap estimates of the misclassification error. The results depend on the data of the clinical study and the given size of the bootstrap sample.

Simulation based analysis of automated, classification of medical images.

OBJECTIVES: The ability of various classifiers to discriminate between normal and glaucomatous eyes based on features derived from automated analysis of laser scanning images of the eye background is investigated. METHODS: To compare the classifiers without over-optimization for a given dataset, we use a simulation model to create topography images. We designed three different simulation setups as model of extreme situations and medical subgroups. RESULTS: Neither linear nor tree-based classifiers are ideal for all setups. The most robust performance is obtained by a combination of both, so-called Double-Bagging. Classification of real data from a case-control study shows best results with Double-Bagging. All results obtained with the analysis method extracting features automatically are worse than those obtained by the same classifiers but with features derived from an analysis method that requires intervention of a physician. CONCLUSIONS: Robust classification results for classification of laser scanning images obtained with the Heidelberg Retina Tomograph are achieved by combined classifiers. The examined automated procedure causes an increased misclassification error compared to the established clinical routine requiring an expert physician's intervention.

In vitro erythrocidal activity of activated spleen cells from young and old mice.

We have recently reported that activated mouse spleen mononuclear cells (MNCs) efficiently lyse autologous erythrocytes in vitro (Saxena and Chandrasekhar, 2000). In the present study, we have investigated erythrocyte-depleting ability (EDA) of spleen MNCs from young and old mice. Time kinetics of survival of erythrocytes in mitogen-activated spleen cell cultures indicated that the erythrocyte depletion was significantly faster in young spleen cell cultures than in the old. Poorer EDA of old MNCs was in spite of the fact that the susceptibility to lysis actually increased in erythrocytes from old mice. Erythrocytes opsonized by a hamster anti mouse Fas monoclonal antibody, were destroyed with a much greater efficiency by young MNCs, whereas the corresponding effect of opsonization was only moderate for old MNCs. Depletion of macrophages from MNC preparations by plastic adherence as well as carbonyl-iron and magnet treatment had a marginal if any effect on EDA of young and old mouse MNCs, indicating that a lower lymphocyte-associated erythrocidal activity as one of the factors responsible for overall lower EDA associated with spleen derived MNCs of old mice.

Cytolytic activity of mitogen activated old and young mouse spleen cells against tumor target cells expressing high or low levels of Fas antigen.

Sensitivity of Fas expressing tumor cells (high levels in Hut78 & Jurkat; low levels in P815) toward the cytotoxic Con-A (5 microg/ml) activated spleen cells from young (12 to 16 week old males) and old (2 year old males) mice were studied. The spleen cells from young mice activated for a day showed high levels of cytotoxic activity against Hut78 and Jurkat cell lines but not against P815 cells. The cytotoxic activity against P815 cells were detected in the spleen cells from old but not young mice following a longer period of Con-A activation (three days). Comparable levels of cytotoxic activity against Hut78 and Jurkat cells were observed in the spleen cells from both young and old mice following three days of activation. Treatment of Hut78 cells with anti-Fas antibody affected the tumor cells become resistant against the cytotoxic activity of the spleen cells from young mice in a dose dependent manner however P815 cells were not affect by the anti-Fas antibody treatment. These results show that there are differences in the sensitivity of target tumor cells toward Con-A induced cytotoxic spleen cells from young and old mouse. Mitogen-induced cytotoxic lymphocytes from young mouse spleen appear to kill targets through mechanisms involving Fas antigen, specially, in early stage (1 day) of activation. Old mouse spleen cells generated high levels of cytotoxic cells in later phase (3 days), which appear to kill through Fas-unrelated mechanisms.

Serum antibodies to HIV-1 are produced post-measles virus infection: evidence for cross-reactivity with HLA.

Convalescent sera obtained from patients who were recently recovered from an acute measles virus infection were tested for the presence of anti-HIV-1 antibodies by Western blot analysis. While 16% (17/104) of control sera displayed reactive bands to a variety of HIV proteins, 62% (45/73) of convalescent sera demonstrated immunoreactive bands corresponding to HIV-1 Pol and Gag, but not Env antigens. This cross-reactivity appears to be the result of an active measles infection. No HIV-1 immunoblot reactivity (0/10) was observed in sera obtained from young adults several weeks after a combined measles, mumps, and rubella (MMR) vaccination. Interestingly, examination of anti-HLA typing sera specific for either class I and class II molecules revealed that 46% (19/41) of these sera contained cross-reactive antibodies to HIV-1 proteins. Absorption of measles sera with mixed lymphocyte reaction (MLR)-activated lymphocytes and/or HIV-1 recombinant proteins significantly decreased or removed the presence of these HIV-1-immunoreactive antibodies. Together, these findings suggest that the immune response to a natural measles virus infection results in the production of antibodies to HIV-1 and possibly autoantigens.

Immunological aspects of aging and malnutrition: consequences and intervention with nutritional immunomodulators.

As knowledge of molecular and cellular mechanisms of development and aging is elucidated, the need to understand the relationships among tissues, organ systems, health habits, nutrition, physical activity, and environmental factors on successful aging becomes more explicit. Progress in our understanding of how the immune system functions and responds with other factors, such as aging and nutrition, is spawning significant inroads to achieving a successful old age.