Ion-ion dynamic structure factor, acoustic modes, and equation of state of two-temperature warm dense aluminum.

The ion-ion dynamical structure factor and the equation of state of warm dense aluminum in a two-temperature quasiequilibrium state, with the electron temperature higher than the ion temperature, are investigated using molecular-dynamics simulations based on ion-ion pair potentials constructed from a neutral pseudoatom model. Such pair potentials based on density functional theory are parameter-free and depend directly on the electron temperature and indirectly on the ion temperature, enabling efficient computation of two-temperature properties. Comparison with ab initio simulations and with other average-atom calculations for equilibrium aluminum shows good agreement, justifying a study of quasiequilibrium situations. Analyzing the van Hove function, we find that ion-ion correlations vanish in a time significantly smaller than the electron-ion relaxation time so that dynamical properties have a physical meaning for the quasiequilibrium state. A significant increase in the speed of sound is predicted from the modification of the dispersion relation of the ion acoustic mode as the electron temperature is increased. The two-temperature equation of state including the free energy, internal energy, and pressure is also presented.

Ceftriaxone attenuates acute cocaine-evoked dopaminergic neurotransmission in the nucleus accumbens of the rat.

BACKGROUND AND PURPOSE: Ceftriaxone is a ß-lactam antibiotic and glutamate transporter activator that reduces the reinforcing effects of psychostimulants. Ceftriaxone also reduces locomotor activation following acute psychostimulant exposure, suggesting that alterations in dopamine transmission in the nucleus accumbens contribute to its mechanism of action. In the present studies we tested the hypothesis that pretreatment with ceftriaxone disrupts acute cocaine-evoked dopaminergic neurotransmission in the nucleus accumbens. EXPERIMENTAL APPROACH: Adult male Sprague-Dawley rats were pretreated with saline or ceftriaxone (200 mg kg(-1) , i.p. × 10 days) and then challenged with cocaine (15 mg kg(-1) , i.p.). Motor activity, dopamine efflux (via in vivo microdialysis) and protein levels of tyrosine hydroxylase (TH), the dopamine transporter and organic cation transporter as well as α-synuclein, Akt and GSK3ß were analysed in the nucleus accumbens. KEY RESULTS: Ceftriaxone-pretreated rats challenged with cocaine displayed reduced locomotor activity and accumbal dopamine efflux compared with saline-pretreated controls challenged with cocaine. The reduction in cocaine-evoked dopamine levels was not counteracted by excitatory amino acid transporter 2 blockade in the nucleus accumbens. Pretreatment with ceftriaxone increased Akt/GSK3ß signalling in the nucleus accumbens and reduced levels of dopamine transporter, TH and phosphorylated α-synuclein, indicating that ceftriaxone affects numerous proteins involved in dopaminergic transmission. CONCLUSIONS AND IMPLICATIONS: These results are the first evidence that ceftriaxone affects cocaine-evoked dopaminergic transmission, in addition to its well-described effects on glutamate, and suggest that its ability to attenuate cocaine-induced behaviours, such as psychomotor activity, is due in part to reduced dopaminergic neurotransmission in the nucleus accumbens.

Periodontal conditions in vegetarians: a clinical study.

BACKGROUND/OBJECTIVES: Investigations about possible correlations between vegetarian diet and periodontal conditions are rare and characterized by small case numbers. The aim of this clinical study was to investigate the influence of a vegetarian diet on periodontal parameters with an appropriate sample size. SUBJECTS/METHODS: A total of 200 patients, 100 vegetarians and 100 non-vegetarians, were included in the study. All patients were examined including a full mouth assessment of the periodontal and dental conditions. In addition, a questionnaire was handed out to ask for patients' oral hygiene habits and level of education. For statistical analysis the Mann-Whitney Test (χ(2) for analysis of the questionnaire) was applied (level of significance: P<0.05). RESULTS: Well known periodontal risk factors like age, gender and smoking habits were equally distributed within each group (71 females, 29 males, respectively and 10 smokers in each group; mean age: 41.45 years vegetarians versus 41.72 years non-vegetarians). Vegetarians had significantly lower probing pocket depths (P=0.039), bleeding on probing (P=0.001), periodontal screening index (P=0.012), a better hygiene index (P<0.001) and less mobile teeth (P=0.013). Dental examinations revealed significantly less missing teeth (P=0.018) but also more decayed (P=0.001) and eroded (P=0.026) teeth in vegetarians. Furthermore, vegetarians had a higher level of education (P<0.001), but visited dentists significantly less frequent. CONCLUSIONS: Vegetarians revealed better periodontal conditions (less inflammation signs, less periodontal damage and a better dental home care). However, it should be considered that vegetarians are not only avoiding meat in their nutrition but are also characterized by an overall healthier life style.

[Reinnervation and neurostimulation of the larynx]. / Reinnervation und Neurostimulation des Kehlkopfs.

Dynamic rehabilitation of vocal fold paralysis (VFP) should receive more emphasis in the future. In unilateral immobility with signs of atrophy and wide glottal gap, non-selective reinnervation with ansa cervicalis may become an alternative to augmentation and thyroplasty. For bilateral VFP progress has been made in the concepts of selective reinnervation and neurostimulation (pacing). These new therapies have the potential to restore near normal respiration-without compromising the voice quality-and may contribute to the development of larynx transplantation surgery.

[Staging with 18F-FDG-PET/CT influences stage-specific survival in advanced non-small cell lung cancer (NSCLC)]. / Der Einfluss des F-18-FDG-PET/CT auf das stadienbezogene Gesamtüberleben beim fortgeschrittenen nicht-kleinzelligen Lungenkarzinom (NSCLC).

BACKGROUND: PET/CT investigation with 18F-fluorodeoxyglucose (FDG) has a high sensitivity (89 - 100 %) and good specificity (79 - 95 %) for the diagnosis of NSCLC. Currently, it is mainly used in preoperative staging. This leads in approximately 15 % of these cases to the diagnosis of metastatic disease that was neither clinically suspected nor seen in previously performed conventional imaging. We hypothesised that including these cases in the palliative stage IV group would have an influence on overall survival. AIM: The aim of this study was to compare the overall survival (OS) of patients with stage IV NSCLC who underwent FDG-PET/CT staging with patients in whom conventional imaging procedures were performed. METHODS: We analysed the OS of all stage IV NSCLC patients diagnosed in our clinic in 2009 (n = 254), 96/254 (38 %) patients were staged with PET/CT and 158/254 (62 %) with conventional imaging (CT group). Survival data were compared by Kaplan-Meier statistics. RESULTS: Patients in the PET/CT group were younger (65 ± 11) than in the CT group (68 ± 10 years; p = 0.008). The median OS of all patients was 246 (range: 217 - 275) days; 338 (range: 247 - 429) days in the PET/CT group and 207 (range: 161 - 253) days in the CT group (p = 0.001), stating a difference of 131 days (4.4 months) in median OS. CONCLUSION: The use of FDG-PET/CT staging mainly in the preoperative setting leads to stage migration of patients with a better prognosis into the worst stage (IV) and thus longer survival within this subgroup. This survival benefit is unrelated to treatment and needs to be addressed in future studies.

Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial.

BACKGROUND: To compare capecitabine/cisplatin with 5-fluorouracil/cisplatin as first-line treatment for advanced gastric cancer (AGC). PATIENTS AND METHODS: In this randomised, open-label, phase III study, patients received cisplatin (80 mg/m(2) i.v. day 1) plus oral capecitabine (1000 mg/m(2) b.i.d., days 1-14) (XP) or 5-FU (800 mg/m(2)/day by continuous infusion, days 1-5) (FP) every 3 weeks. The primary end point was to confirm noninferiority of XP versus FP for progression-free survival (PFS). RESULTS: A total of 316 patients were randomised to XP (n = 160) or FP (n = 156). In the per-protocol population, median PFS for XP (n = 139) versus FP (n = 137) was 5.6 versus 5.0 months. The primary end point was met with an unadjusted hazard ratio (HR) of 0.81 [95% confidence interval (CI) 0.63-1.04, P < 0.001 versus noninferiority margin of 1.25]. Median overall survival was 10.5 versus 9.3 months for XP versus FP (unadjusted HR = 0.85, 95% CI 0.64-1.13, P = 0.008 versus noninferiority margin of 1.25). The most common treatment-related grade 3/4 adverse events in XP versus FP patients were as follows: neutropenia (16% versus 19%), vomiting (7% versus 8%), and stomatitis (2% versus 6%). CONCLUSIONS: XP showed significant noninferiority for PFS versus FP in the first-line treatment of AGC. XP can be considered an effective alternative to FP.

[Juvenile laryngeal papillomatosis--immunisation with the polyvalent vaccine gardasil]. / Juvenile Larynxpapillomatose--Impfung mit dem polyvalenten Spaltimpfstoff Gardasil.

Juvenile laryngeal papillomatosis is a rare condition caused by human papilloma virus (HPV). In cases with rapid recurrences permanent impairments of voice and breathing are almost inevitable due to the frequent need of debulking surgeries. Efforts to lower the recurrence rate comprise the adjuvant use of interferon alpha, local cidofovir, photodynamic therapy or mumps vaccination. In the present case we tried to positively influence the aggressive course of disease in a two year old boy by immunisation with the quadrivalent HPV vaccine Gardasil(R). Chromogenic in-situ hybridisation analysis and polymerase chain reaction (PCR) of lesion tissue showed simultaneous infection with the HPV-Types 6 and 11. After the third immunisation the disease became stable. No further surgery was necessary for the last ten months. The risk profile of this adjuvant treatment is low. We think it worth to initiate a multicentre trial to prove a benefit of this treatment even if no complete virus elimination can be achieved.

Microglial activation in white matter lesions and nonlesional white matter of ageing brains.

White matter lesions (WML), a common feature in brain ageing, are classified as periventricular (PVL) or deep subcortical (DSCL), depending on their anatomical location. Microglial activation is implicated in a number of neurodegenerative diseases, but the microglial response in WML is poorly characterized and its role in pathogenesis unknown. We have characterized the microglial response in WML and control white matter using immunohistochemistry to markers of microglial activation and of proliferation. WML of brains from an unbiased population-based autopsy cohort (Medical Research Council's Cognitive Function and Ageing Study) were identified by post mortem magnetic resonance imaging and sampled for histology. PVL contain significantly more activated microglia, expressing major histocompatibility complex (MHC) class II and the costimulatory molecules B7-2 and CD40, than either control white matter (WM) or DSCL. Furthermore, we show that significantly more microglia express the replication licensing protein minichromosome maintenance protein 2 within PVL, suggesting this is a more proliferation-permissive environment than DSCL. Although microglial activation occurs in both PVL and DSCL, our findings suggest a difference in pathogenesis between these lesion-types: the ramified, activated microglia associated with PVL may reflect immune activation resulting from disruption of the blood brain barrier, while the microglia within DSCL may reflect an innate, amoeboid phagocytic phenotype. We also show that microglia in control WM from lesional cases express significantly more MHC II than control WM from nonlesional ageing brain, suggesting that WML occur in a 'field-effect' of abnormal WM.

[Olfactory dysfunction. Epidemiology, pathophsiological classification, diagnosis and therapy]. / Riechstörungen. Epidemiologie, pathophysiologische Klassifikation, Diagnose und Therapie.

The present manuscript is the result of a collaborative effort within the framework of the Working Group of Olfactology and Gustology of the German Society for ENT, Head and Neck Surgery. It provides a comprehensive overview about the current views on the epidemiology, terminology, diagnostics, and therapy of olfactory dysfunction, and aims to offer a framework for the standardized procedures for the diagnosis and therapy of olfactory disorders.

National guideline for the management of suspected sexually transmitted infections in children and young people.

The Children Act 1989 defines a child as "a person who has not yet reached 18 years of age." In England, Wales, and Scotland the present age of consent for heterosexual and homosexual sex is 16 years and in Northern Ireland it is 17 years. The proportion of young people who report heterosexual intercourse before the age of 16 years increased in the 1990s compared with the previous decade.

Provision of Chlamydia trachomatis screening in family planning clinics and emergency contraception in genitourinary medicine clinics: a collaborative cross-speciality survey.

Two surveys were undertaken to review (1) provision of Chlamydia trachomatis screening by family planning (FP) clinics in the London region and (2) access to emergency contraception (EC) from genitourinary#10; medicine (GUM) clinics within the former North Thames region. The findings from the first survey suggest that there is insufficient screening (and treatment) in vulnerable groups attending FP clinics. Results#10; from the second survey show that hormonal EC is widely available from within GUM clinics, and those clinics also provide a range of other contraception services. However, these details may not be widely#10; recognised either by policymakers or the general public. #10;

[Medicolegal screening of olfactory function]. / Zur Durchführung präoperativer Riechtests aus medicolegaler Sicht.

Prior to nose surgery the birhinal ability to smell should be tested routinely. From the medico-legal point of view a short screening-test consisting of 5 or 8 test items is not sufficient. It is recommended to use an identification test with 12 or 16 items. The results of these tests taken together with the patients' self estimation, the patients' history and the rhinoscopic findings offer a satisfactory evaluation of the patients' ability to smell in most cases. In case of discrepancies a more detailed test determining the TDI-value is recommendable. If the 16-identification test is used, it is sufficient to add the values of the threshold and the discrimination measurements with the "Sniffin' Sticks" to complete a full TDI score.

Heterogeneity of O6-alkylguanine DNA-alkyltransferase expression in human breast tumours.

An important determinant of cellular resistance to chemotherapeutic O6-alkylating agents, which comprise methylating and chloroethylating agents, is the ability of cells to repair alkylation damage at the O6-position of guanine in DNA. This is achieved by a specific DNA repair enzyme O6-alkylguanine DNA-alkyltransferase. In this study O6-alkylguanine DNA-alkyltransferase expression was measured in human breast tumours using both biochemical and immunohistochemical techniques. O6-alkylguanine DNA-alkyltransferase activity was then compared with known clinical prognostic indices to assess the potential role of O6-alkylguanine DNA-alkyltransferase in predicting the behaviour of this common malignancy. The application of both biochemical and immunohistochemical techniques was feasible and practical. Most breast tumours expressed high levels of O6-alkylguanine DNA-alkyltransferase. Immunohistochemical analysis showed marked variation in expression not only between individuals but also within individual tumours, and in the same patient, between metastases and between primary tumour and metastatic site. O6-alkylguanine DNA-alkyltransferase activity in tissue extracts significantly correlated not only with immunohistochemical staining intensity determined by subjective quantitation, but also with measures of protein levels using a computerised image analysis system including mean grey (P<0.001), percentage of cells positive for O6-alkylguanine DNA-alkyltransferase (P<0.001), and integrated optical density (P<0.001). O6-alkylguanine DNA-alkyltransferase expression did not correlate with any of the established clinical prognostic indicators for current treatment regimens. However, immunohistochemical offers a rapid and convenient method for assessing potential utility of O6-alkylating agents or O6-alkylguanine DNA-alkyltransferase inactivating agents in future studies of breast cancer treatment.

Preliminary data on biodistribution and dosimetry for therapy planning of somatostatin receptor positive tumours: comparison of (86)Y-DOTATOC and (111)In-DTPA-octreotide.

The somatostatin analogue (90)Y-DOTATOC (yttrium-90 DOTA- D-Phe(1)-Tyr(3)-octreotide) is used for treatment of patients with neuroendocrine tumours. Accurate pretherapeutic dosimetry would allow for individual planning of the optimal therapeutic strategy. In this study, the biodistribution and resulting dosimetric calculation for therapeutic exposure of critical organs and tumour masses based on the positron emission tomography (PET) tracer (86)Y-DOTATOC, which is chemically identical to the therapeutic agent, were compared with results based on the tracer commonly used for somatostatin receptor scintigraphy, (111)In-DTPA-octreotide (indium-111 DTPA- D-Phe(1)-octreotide, OctreoScan). Three patients with metastatic carcinoid tumours were investigated. Dynamic and static PET studies with 77-186 MBq (86)Y-DOTATOC were performed up to 48 h after injection. Serum and urinary activity were measured simultaneously. Within 1 week, but not sooner than 5 days, patients were re-investigated by conventional scintigraphy with (111)In-DTPA-octreotide (110-187 MBq) using an equivalent protocol. Based on the regional tissue uptake kinetics, residence times were calculated and doses for potential therapy with (90)Y-DOTATOC were estimated. Serum kinetics and urinary excretion of both tracers showed no relevant differences. Estimated liver doses were similar for both tracers. Dose estimation for organs with the highest level of radiation exposure, the kidneys and spleen, showed differences of 10.5%-20.1% depending on the tracer. The largest discrepancies in dose estimation, ranging from 23.1% to 85.9%, were found in tumour masses. Furthermore, there was a wide inter-subject variability in the organ kinetics. Residence times (tau(organs)) for (90)Y-DOTATOC therapy were: tau(liver) 1.59-2.79 h; tau(spleen) 0.07-1.68 h; and tau(kidneys) 0.55-2.46 h (based on (86)Y-DOTATOC). These data suggest that dosimetry based on (86)Y-DOTATOC and (111)In-DTPA-octreotide yields similar organ doses, whereas there are relevant differences in estimated tumour doses. Individual pretherapeutic dosimetry for (90)Y-DOTATOC therapy appears necessary considering the large differences in organ doses between individual patients. If possible, the dosimetry should be performed with the chemically identical tracer (86)Y-DOTATOC.

Screening for sexually transmitted infections in children and adolescents in the United Kingdom: British Co-operative Clinical Group.

Our objectives were (1) to assess the number of young people aged under 16 years attending genitourinary medicine (GUM) departments in the UK in 1998; (2) to identify clinical activity and policy; (3) to determine the knowledge and training needs of healthcare professionals within GUM providing care for this client group. In July 1999 a questionnaire was circulated via the 18 regional British Co-operative Clinical Group (BCCG) representatives to the consultants in charge of all 197 main GUM departments in the UK. One hundred and sixty out of 197 (81%) completed questionnaires were returned and analysed. The reported number of under-16-year-olds attending in 1998 varied considerably between clinics; for females ranging from 0 to 256 and for males between 0 and 50, with a male to female ratio of 1:4.4. The majority of responding clinics, 139/160 (87%) had been involved in the screening of abused children/adolescents for sexually transmitted infections (STIs). Most clinics were prepared to screen for STI (86%), HIV test (79%) and assess contraceptive needs (50%) in this age group. Staff involved in care included health advisers (74), nurses (59), and doctors (138) in the responding clinics. Only 31/160 clinics (19%) had a written policy for the management of children/adolescents attending their clinic. The majority of respondents were aware of their child protection policy [122/154 (79%)] and designated child sexual abuse doctor, [125/157 (80%)] in their district. When questioned on previous and current training needs, 134/160 (84%) respondents identified their need for further training in the area of adolescent sexual health and 124/160 (78%) in child sex abuse. The publication Physical Signs of Sexual Abuse in Children, was known to 112/160 (70%) respondents, of whom 58/112 (52%) who answered this question had read the publication. Genitourinary physicians in the UK are aware of the increasing number of children and adolescents accessing their services, and recognize the need to identify those in abusive situations. Written policies dealing with children and adolescents in GUM clinics in the UK are lacking. This needs to be rectified urgently. This survey identifies that further training in the field of child sexual abuse and adolescent sexual health would be welcomed by the respondents.

[Therapy monitoring with 2-(18F)-FDG positron emission tomography after neoadjuvant radiation treatment of mouth carcinoma]. / Therapiemonitoring mittels 2-[18F]-FDG-Positronenemissionstomographie nach neoadjuvanter Strahlenbehandlung des Mundhöhlenkarzinoms.

BACKGROUND: Combined protocols of radiation therapy and surgical resection, as applied in advanced oral cancer, rely on objective and early assessment of treatment response to radiation therapy. Non-responders require immediate radical salvage surgery even in spite of substantial operative risks, while complete or subtotal response may give reasons for continuing the conservative approach. Therefore, we investigated radiation response by FDG-PET for early monitoring of oral cancer. PATIENTS AND METHODS: In 30 patients with advanced stages of oral cancer (Table 1), FDG-PET (Siemens, ECAT EXACT 922) was performed within 4 weeks after completion of preoperative radiation therapy (36 Gy). SUV of tumor regions were compared to the histologic degree of tumor regression in complete resection specimens. Statistic evaluation included correlation analysis of SUV vs tumor regression and ROC analysis for SUV cut-off values. RESULTS: While low FDG accumulation was found in tumors with histological complete remission (2.3 +/- 0.4) as well as in cases of residual tumor (3.4 +/- 1.8), high FDG uptake was a rather specific indicator of vital tumor tissue (Figure 2). Significant correlation (p = 0.045) between postradiotherapeutic FDG-uptake and histological tumor regression was recognized. A SUV > 2.75 as a clinically practicable threshold value for the identification of residual vital tumor resulted in a specificity of 88%, sensitivity of 68%, a positive predictive value of 94% and a negative predictive value of 50% (Figure 3). Based on our actual follow-up data we could not confirm a significant correlation between postradiotherapeutic SUV and patients' survival. CONCLUSION: Within a standardized protocol, FDG-PET recognize treatment response to radiation therapy in oral squamous cell carcinoma with a reasonable specificity and thus provides a basis for further therapeutic decisions. An increased SUV (> 2.75) may be the rational to justify an aggressive surgical approach even when patients face substantial surgical or anesthesiological risk. However, the posttherapeutic pattern of glucose uptake varies with the applied treatment modalities and has to be explored for the protocol applied.

[Unusual manifestation of zoster sine herpete as unilateral caudal cranial nerve syndrome]. / Ungewöhnliche Manifestation eines Zoster sine herpete als unilaterales kaudales Hirnnervensyndrom.

Multiple lower cranial nerve palsies are a rare complication following varicella zoster virus (VZV) reactivation, especially if typical herpetic eruptions are lacking. We report a case of a 45-year-old, immunocompetent male with unilateral involvement of the cranial nerves VIII, IX, X, and XI without skin lesions. Cerebrospinal fluid (CSF) studies revealed mononuclear pleocytosis with intrathecal antibody synthesis against VZV, while polymerase chain reaction (PCR) did not detect VZV or HSV (herpes simplex virus). The patient almost completely recovered after aciclovir administration. VZV reactivation without rash (zoster sine herpete) may lead to multiple cranial nerve palsies. PCR is a useful tool to detect VZV-DNA in CSF, but negative results do not exclude a reactivation. In case of multiple cranial nerve palsies of unknown etiology with mononuclear pleocytosis in CSF tumors of the skull base, meningitis tuberculosis, and meningeosis have to be excluded, and antiviral therapy should be discussed.

4-Year follow-up results of a European prospective randomized study on neoadjuvant hormonal therapy prior to radical prostatectomy in T2-3N0M0 prostate cancer. European Study Group on Neoadjuvant Treatment of Prostate Cancer.

OBJECTIVES: To evaluate the long-term effects of 3-month neoadjuvant hormonal treatment in patients treated by radical prostatectomy for locally confined prostate cancer. METHODS: We report the results of 402 patients (220 with a clinical T2 tumor and 182 with a clinical T3 tumor) of whom 192 randomly received neoadjuvant total androgen deprivation using a LHRH analogue (goserelin) plus flutamide for a period of 3 months and 210 underwent radical prostatectomy only. RESULTS: 'Clinical downstaging' was seen in 30% of cases in the neoadjuvantly treated group (NEO). 'Pathological downstaging' occurred in 7 and 15% of cases in the direct radical prostatectomy (DP) group and the NEO group, respectively (p<0.01). In patients with clinical T2 as well as in patients with clinical T3 tumors, a significant difference in the number of positive margins was shown in favor of the NEO group (cT2, p<0.01; cT3, p = 0.01). This advantage, although there was a trend in favor of the NEO group, specifically in cT2 tumors, did not translate in a significantly better PSA progression rate (p = 0.18). However, when evaluating the local control rate in cT2 tumors, we observed local recurrence in 3 of 102 (3%) patients in the NEO group versus 12 of 114 (11%) patients in the DP group. The difference is statistically significant (p = 0.03). In the cT3 group, this difference was not statistically significant (NEO group: 15 of 87 (17%), and DP group: 21 of 95 (22%) patients; p = 0.41). CONCLUSIONS: In this study, the clinical revelance of pathological downstaging and the lower percentage of patients with positive margins in the neoadjuvantly treated group with a clinical T2 tumor is not confirmed by a lower PSA progression rate. However, this study indicates that there may be a trend that this advantage in favor of the NEO group directly translates into a better local control rate in clinical T2 tumors. Better local control in cT2 tumors is only going to be of relevance if subsequently you can show that there is a better survival for these patients. Unfortunately, this article reports a study which is not yet mature enough to show relevant information. Presently, neoadjuvant therapy should not be given outside clinical research settings.