Increase of RM3/1-positive macrophages in radiation-induced oral mucositis

The purpose of this study was to describe the distribution patterns of various leukocyte subpopulations in the oral mucosa during the course of radiotherapy and to determine whether there are dose-dependent alterations, or any correlation between the clinical stages and the population density of specific leukocytes. The distribution and density of various leukocytes in oral mucosa in 13 head and neck cancer patients were immunohistochemically analysed before radiotherapy at 30 and 60 Gy and compared with the clinical degree of oral mucositis. Antibodies were used which characterized different subtypes of macrophages (27E10, 25F9, RM3/1) and recognized epitopes of granulocytes (CD15) and T cells (CD3, CD4, CD8). The study showed that whereas macrophages reactive with RM3/1 increased significantly at 30 Gy (p<0.01) and showed a further increase at 60 Gy (p<0.01), no significant alterations could be detected in the density of macrophages which stained positively for 27E10 or 25F9. Moreover, the percentage of macrophages reactive with RM3/1 showed a non-linear correlation with the clinical mucositis score (p<0.05). No significant alterations were detected in the percentage of T cells and granulocytes, compared with the values before radiotherapy. In conclusion, radiation-induced mucositis is characterized by features of an intermediate stage of an inflammatory response, suggesting active involvement of down-regulatory macrophages in its pathogenesis.     

Operative Verfahren der Mund-, Kiefer- und Gesichtschirurgie an nach Thiel fixierten Körperspenden

Methods: This study investigates whether human cadavers embalmed according to Thiel can be used for research and education in oral-maxillo-facial surgery. Different surgical approaches were tested on such cadavers. The usability of the specimen was judged jointly by anatomists and surgeons. Color, structure, and consistency of the different tissues were comparable to vital conditions. Thiel’s embalming technique applied to human cadavers provides an optimal basis for research and for basic and postgraduate medical education.     

Vascular basis of mucosal color

Background

It has been hypothesized that prematurity and adjunctive neonatal care is 'a priori' a risk for disturbances of palatal and orofacial development which increases the need for later orthodontic or orthognathic treatment. As results on late consequences of prematurity are consistently contradictory, the necessity exists for a fundamental analysis of existing methodologies, confounding factors, and outcomes of studies on palatal development in preterm and low birthweight infants.

Method

A search of the literature was conducted based on Cochrane search strategies including sources in English, German, and French. Original data were recalculated from studies which primarily dealt with both preterm and term infants. The extracted data, especially those from non-English paper sources, were provided unfiltered in tables for comparison (Parts 1 and 2).

Results

Morphology assessment of the infant palate is subject to non-standardized visual and metrical measurements. Most methodologies are inadequate for measuring a three-dimensional shape. Several confounding factors were identified as causes contributing to disturbances of palatal and orofacial development.

Conclusion

Taking into account the abovementioned shortcomings, the following conclusions may be drawn for practitioners and prospective investigators of clinical studies. 1) The lack of uniformity in the anatomical nomenclature of the infant's palate underlines the need for a uniform definition. 2) Metrically, non-intubated preterm infants do not exhibit different palatal width or height compared to matched term infants up to the corrected age of three months. Beyond that age, no data on the subject are currently available. 3) Oral intubation does not invariably alter palatal morphology of preterm and low birthweight infants. 4) The findings on palatal grooving, height, and asymmetry as a consequence of orotracheal intubation up to the age of 11 years are inconsistent. 5) Metrically, the palates of orally intubated infants remain narrower posteriorly, beginning at the second deciduous molar, until the age of 11 years. Beyond that age, no data on the subject are currently available. 6) There is a definite need for further, especially metrical, longitudinal and controlled trials on palatal morphology of preterm and low birthweight infants with reliable measuring techniques. 7) None of the raised confounding factors for developmental disturbances may be excluded until evident results are presented. Thus, early orthodontic and logopedic control of formerly premature infants is recommended up to the late mixed dentition stage.     

Prognostic value of histobiological factors (malignancy grading and AgNOR content) assessed at the invasive tumour front of oral squamous cell carcinomas.

Tumour cells at the invasive front of carcinomas have been found to differ substantially from the rest of tumour cells in a variety of human cancers. The present multivariate survival analysis of 94 oral squamous cell carcinomas (OSCCs) revealed that both the argyrophilic nucleolar organizer regions-associated protein (AgNOR) content of invading tumour cells and a multiparametric histopathological tumour front grade were significantly and independently associated with tumour-related death, irrespective of conventional Broders'' grade and clinical stage of the tumours. High tumour front scores and AgNOR content at the invasive OSCC front thus seem to reflect increased malignant potential. Proliferative activity, assessed by standardized AgNOR analysis, most probably represents one of the biological features underlying the usefulness of evaluating the invasive tumour front.     

Multinational study in children and adolescents with newly diagnosed type 1 diabetes: association of age,ketoacidosis, HLA status,and autoantibodies on residual beta‐cell function and glycemic control 12 months after diagnosis

HB Mortensen, PGF Swift, RW Holl, P Hougaard, L Hansen, H Bjoerndalen, CE de Beaufort, M Knip. Multinational study in children and adolescents with newly diagnosed type 1 diabetes: association of age, ketoacidosis, HLA status, and autoantibodies on residual beta‐cell function and glycemic control 12 months after diagnosis. Objective: To identify predictors of residual beta‐cell function and glycemic control during the first 12 months after the diagnosis of type 1 diabetes (T1D). Subjects and Methods: Clinical information and blood samples were collected from 275 children. HbA1c, antibodies, HLA typing and mixed meal‐stimulated C‐peptide levels 1, 6, and 12 months after diagnosis were analyzed centrally. Results: Mean age at diagnosis was 9.1 yr. DKA with standard bicarbonate <15 mmol/L was associated with significantly poorer residual beta‐cell function 1 (p = 0.004) and 12 months (p = 0.0003) after diagnosis. At 12 months, the decline in stimulated C‐peptide levels compared with the levels at 1 month was 69% in the youngest age group and 50% in patients 10 yr and above (p < 0.001). Stimulated C‐peptide at 12 months was predicted by younger age (p < 0.02) and bicarbonate levels at diagnosis (p = 0.005), and by stimulated C‐peptide (p < 0.0001), postmeal blood glucose (p = 0.0004), insulin antibodies (IA; p = 0.02) and glutamic acid decarboxylase antibodies (GADA; p = 0.0004) at 1 month. HbA1c at 12 months was predicted by HbA1c at diagnosis (p < 0.0001), GADA at 1 month (p = 0.01), and non‐white Caucasian ethnicity (p = 0.002). Conclusions: Younger age, ketoacidosis at diagnosis, and IA and GADA 1 month after diagnosis were the strongest explanatory factors for residual beta‐cell function at 12 months. Glycemic control at 12 months was influenced predominantly by ethnicity, HbA1c at diagnosis, and GADA at 1 month.     

Spezifische physiologische und unspezifische psychische Effekte bei der Akupunkturtherapie des Reizdarmsyndroms: Ergebnisse einer randomisierten kontrollierten Studie

Background and aims

The aim was to evaluate the efficacy of acupuncture (AC) in patients with irritable bowel syndrome (IBS). We investigated psychological and neuroendocrinological parameters to meet the demands of the psychosomatic paradigm. In addition, we wanted to examine the impact of perception of bodily sensations on treatment response.

Methods

43 patients with IBS were randomly assigned to receive either AC (n = 22) or sham acupuncture (SAC) (n = 21) using the ”Streitberger needle„. Primary outcome measure was quality of life (QoL) measured with the functional digestive diseases quality of life questionnaire (FDDQL) and a general quality of life questionnaire (SF-36). QoL was measured before AC treatment (t1), after ten treatment sessions (t2) and three months after treatment (t3). Secondary outcome measures were parameters of the autonomic nervous system (ANS) which were evaluated with tilt-table manoeuvres at t1 and t2. Additionally, salivary cortisol was measured at t1 ant t2. Perception of bodily sensation was measured at t1 with the ”Perception of Bodily Sensation„ (PBS) questionnaire.

Results

QoL improved in both groups (p = 0,022). However, there were no group differences in QoL improvements between AC and SAC. Salivary cortisol decreased in both groups (F = 10,55; p = 0,006). However, the decrease was more pronounced in the AC group (F = 4,07; p = 0,033). Heart rate response decreased during orthostatic stress in the AC group while it increased in the SAC group (group difference: F = 9,23; p = 0,005), indicating an increased parasympathetic tone in the AC group. Improvement of pain was positively associated with increased parasympathetic tone in the AC group (r² =0,40; F = 10,1; p = 0,006), but not in the SAC group. High PBS was associated with lower QoL before and after treatment (p = 0,033).

Conclusions

The psychosomatic study design made it possible to detect differentiated acupuncture effects. QoL improvement seems to be due to unspecific effects and physiological changes are likely to be induced specifically by AC. Thus, different mechanisms may be involved in sham and real-AC mediated improvements. Patients with high PBS show a more unfavourable course of treatment independently of the kind of acupuncture treatment.     

Protein biochips: the calm before the storm

The growth of protein biochip technology is on a different trajectory than other drug discovery and development technologies, such as DNA sequencing and high-throughput screening, where output per experiment has grown exponentially. By contrast, experimentation with protein biochips immediately hit barriers in output because of the limited availability of content and the challenges of running biochemical experiments on the surface of a biochip. Nevertheless, the industry has been making significant progress recently by launching new platforms with focused content and new multiplexed biochemical assays. However, this success might only represent the calm before the storm. Over the long-term, protein biochips have the potential to change the drug discovery and development process at the molecular level. The output and throughput of protein biochips could enable researchers to change from the traditional model of one target-one drug to a new model of evaluating one or more potential drugs against a panel of relevant molecular targets from a complex disease state.     

Pharmacokinetic evaluation of armodafinil for the treatment of bipolar depression

Introduction: Bipolar disorder is a psychiatric illness with recurring episodes of mania and depression. Armodafinil , the R-enantiomer of modafinil, approved for treating excessive sleepiness associated with narcolepsy, obstructive sleep apnea and shift work disorder, is possibly effective as an adjunctive treatment for bipolar depression. Areas covered: This review covers the pharmacokinetics of armodafinil, with an emphasis on its use in bipolar depression. Its clinical efficacy in the treatment of bipolar depression is evaluated, along with current data regarding its safety and tolerability. Expert opinion: One placebo-controlled trial is available, in which armodafinil was efficacious as an adjunctive treatment in bipolar depression. Armodafinil shows a linear pharmacokinetic profile over a broad dose range of 50 - 400 mg (maximal plasma concentration and area under concentration-time curve). Compared with modafinil, an equivalent dose of armodafinil attains higher blood concentrations 4 - 6 h post-dose. The possibility of drug interactions is generally low, although interactions have been shown with some drugs used in bipolar disorder, through mild CYP3A4-induction and CYP2C19-inhibition. Armodafinil is well tolerated and presents a possible new treatment option for bipolar depression. However, further investigation is still needed in order to confirm its efficacy and to clarify its role in the treatment of bipolar depression.     

Supplemental transscleral diode laser cyclophotocoagulation after aqueous shunt placement in refractory glaucoma

OBJECTIVE: To assess the outcome of supplemental transscleral diode laser cyclophotocoagulation after aqueous tube shunt placement to obtain effective intraocular pressure (IOP) control. DESIGN: Retrospective non-comparative case series. PARTICIPANTS: Twenty-one eyes in 21 subjects with uncontrolled IOP despite the presence of an aqueous tube shunt and maximally tolerated glaucoma medications. INTERVENTION: Supplemental transscleral diode laser cyclophotocoagulation was performed. MAIN OUTCOME MEASURES: Reduction of intraocular pressure and reduction of glaucoma medications. RESULTS: Twelve adults and nine children underwent supplemental transscleral diode cyclophotocoagulation and were followed postoperatively for a mean of 26.9 +/- 13.4 (standard deviation [SD]) months (range, 7-58 months). Average IOP was significantly reduced from a preoperative level of 35.7 +/- 14.7 (SD) mmHg to a postoperative level of 13.6 +/- 7.1 (SD) mmHg (P < 0.001) with the mean number of medications significantly reduced to 1.5 +/- 1.3 (SD) (P < 0.001). Seven subjects (33%) had additional laser treatment to achieve IOP control. Six subjects who were therapy failures included three who developed no light perception in the setting of proliferative diabetic retinopathy, one subject with chronic angle-closure glaucoma who gradually developed no light perception after refusing further treatment or medication, and two subjects who developed retinal detachments. One child who was a qualified success underwent enucleation and debulking of an enlarging neurofibroma that caused significant proptosis and disfigurement. CONCLUSIONS: In cases of glaucoma that are uncontrolled despite a glaucoma aqueous tube shunt and multiple medications, adjunctive transscleral diode cyclophotocoagulation treatment(s) is a viable option to lower IOP.