Human V5/MT+: comparison of functional and cytoarchitectonic data

To date, the delineation of the human visual “motion area” still relies on functional paradigms originally devised to identify monkey area MT. Using fMRI, we have identified putative human area V5/MT+ in normals by modelling the BOLD responses to alternating radially moving and stationary dot patterns. Functional activations were compared with cytoarchitectonic probability maps of its putative correlate area hOc5, which was calculated based upon data from histological sections of ten human post-mortem brains. Bilateral visual cortex activations were seen in the single subject dynamic versus stationary contrasts and in the group random-effects analysis. Comparison of group data with area hOc5 revealed that 19.0%/39.5% of the right/left functional activation was assigned to the right/left hOc5. Conversely, 83.2%/53.5% of the right/left hOc5 was functionally activated. Comparison of functional probability maps (fPM) with area hOc5 showed that 28.6%/18.1% of the fPM was assigned to hOc5. In turn, 84.9%/41.5% of the area hOc5 was covered by the respective fPM. Thus, random-effects data and fPMs yielded similar results. The present study shows for the first time the correspondence between the functionally defined human V5/MT+ and the post-mortem cytoarchitectonic area hOc5.     

Intraabdominal infections and gut origin sepsis

Intraabdominal postoperative or posttraumatic infections remain a major threat to life in spite of generation after generation of increasingly effective antimicrobial drugs indicating the importance of immunological host defense failure following major trauma or surgical complications. The spectrum of infectious postoperative or posttraumatic complications can, in part, be explained by pathogenic factors inherent to the methodology of modern surgical intensive care and techniques. This report presents a survey of the historical background as well as current concepts of the multiple systems organ failure syndrome as related to postoperative or posttraumatic intraabdominal infectious complications. The pathophysiology of nosocomial infectious complications in the intensive care unit setting is analyzed. The concept of gut origin sepsis is presented and possible preventive and therapeutic actions discussed. A judicious use of antimicrobial drugs on strict indications is emphasized as is the importance of increased knowledge of the interactions between the gut flora, antibiotics, and absence of enteral nutrition.

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Resumen Las infecciones intraabdominales postoperatorias o postraumáticas siguen representando una amenaza grave para la vida a pesar de generación tras generación de drogas antimicrobianas de creciente efectividad, lo cual señala la importancia de la falla de los mecanismos inmunes de defensa del huésped que se presenta después de trauma mayor o acompanando las complicaciones quirúrgicas. El espectro de las complicaciones infecciosas postoperatorias o postraumáticas puede ser explicado en parte por factores patogénicos inhérentes a la tecnología y metodología del moderno cuidado intensivo del paciente en estado crítico. El presente informe reporta una revisión de los antecedentes históricos y de los conceptos actuales sobre el sindrome de falla orgánica multisistémica relacionado con complicaciones infecciosas intraabdominales postoperatorias o postraumáticas. Se analiza la patofisiología de las complicaciones infecciosas nosocomiales en el marco de la unidad de cuidado intensivo. Se hace énfasis sobre el uso juicioso de drogas antimicrobianas según indicaciones estrictas, asi como sobre la importancia de un mayor conocimiento sobre las interacciones entre la flora intestinal, los antibióticos, y la ausencia de nutrición enterai.

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Résumé Les infections intra-abdominales postopératoires ou post-traumatiques continuent de menacer le pronostic vital malgré une amélioration constante des antibiotiques ce qui met l'accent sur l'échec des moyens de défense immunologiques après les traumatismes majeurs ou les complications chirurgicales. Le spectre des complications infectieuses postopératoires ou post-traumatiques peut, en partie, être expliqué par des facteurs pathogéniques inhérents à la méthode des soins intensifs et techniques modernes. Ce travail présente l'historique et les concepts actuels de défaillance polyviscérale en rapport avec des complications infectieuses intra-abdominales postopératoires ou post-traumatiques. La pathophysiologie des complications infectieuses nosocomiales dans l'unité des soins intensifs est analysée. La conception de sepsis d'origine intestinale est présentée et les actions préventive et thérapeutique sont discutées. L'utilisation judicieuse des antibiotiques est soulignée, ainsi que les interactions entre la flore intestinale, les antibiotiques et l'absence de nutrition entérale.

     

Antitumor vaccination of patients with glioblastoma multiforme: a pilot study to assess feasibility, safety, and clinical benefit.

PURPOSE: Prognosis of patients with glioblastoma is poor. Therefore, in glioblastoma patients, we analyzed whether antitumor vaccination with a virus-modified autologous tumor cell vaccine is feasible and safe. Also, we determined the influence on progression-free survival and overall survival and on vaccination-induced antitumor reactivity. PATIENTS AND METHODS: In a nonrandomized study, 23 patients were vaccinated and compared with nonvaccinated controls (n = 87). Vaccine was prepared from patient's tumor cell cultures by infection of the cells with Newcastle Disease Virus, followed by gamma-irradiation, and applied up to eight times. Antitumor immune reactivity was determined in skin, blood, and relapsed tumor by delayed-type hypersensitivity skin reaction, ELISPOT assay, and immunohistochemistry, respectively. RESULTS: Establishment of tumor cell cultures was successful in approximately 90% of patients. After vaccination, we observed no severe side effects. The median progression-free survival of vaccinated patients was 40 weeks (v 26 weeks in controls; log-rank test, P = .024), and the median overall survival of vaccinated patients was 100 weeks (v 49 weeks in controls; log-rank test, P < .001). Forty-five percent of the controls survived 1 year, 11% survived 2 years, and there were no long-term survivors (> or = 3 years). Ninety-one percent of vaccinated patients survived 1 year, 39% survived 2 years, and 4% were long-term survivors. In the vaccinated group, immune monitoring revealed significant increases of delayed-type hypersensitivity reactivity, numbers of tumor-reactive memory T cells, and numbers of CD8(+) tumor-infiltrating T-lymphocytes in secondary tumors. CONCLUSION: Postoperative vaccination with virus-modified autologous tumor cells seems to be feasible and safe and to improve the prognosis of patients with glioblastomas. This could be substantiated by the observed antitumor immune response.     

Immediate Obturation of the Surgical Defect after Partial Maxillectomy in the Endentulous Patient

Closure of the surgical defect immediately after partial maxillectomy is the treatment of choice. The advantages are: maintaining facial contour, rapid re-establishment of speech, swallowing and mastication. A number of methods for the fixation of the immediate obturator in patients without teeth have been described. A new technique is reported where a transnasal wire holds the existing denture in position after partial maxillectomy. The method has been carried out on 7 patients with sino-nasal cancer during the period 1978-1994. The advantages of the technique are that the wire acts as an axis of rotation which together with the sponge in the cavity provide good stability of the denture. There is minimal preoperative laboratory work and simplification in replacing the surgical dressing.     

Disseminated Bartonella henselae disease mimicking Langerhans’ cell histiocytosis

Bartonella henselae, the causative agent of cat‐scratch disease, has been recognized to be responsible for a broad range of clinical syndromes. We report the case of a patient with disseminated B. henselae infection mimicking Langerhans cell histiocytosis at presentation and its successful management with neurosurgery, prolonged antibacterial therapy, and observation.     

Age-specific prevalence of HPV genotypes in cervical cytology samples with equivocal or low-grade lesions

Background:

To define the spectrum of human papillomavirus (HPV) types and establish an age limit for triage HPV testing in atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL).

Materials and methods:

343 liquid-based cytological samples from the population-based screening programme with minor abnormalities were subjected to HPV genotyping (Linear Array, Roche, Basel, Switzerland).

Results:

High-risk human papillomavirus (HR-HPV) was found in 71% of LSIL and 49% of ASCUS cases (P<0.001). High-risk human papillomavirus prevalence was age-dependent in LSIL (P=0.01), with decreasing prevalence until the age of 50 years, followed by a slight increase. Human papillomavirus type 16 was the most common HR-HPV, found in 23% of HPV-positive women. Human papillomavirus type 18 was the sixth most common, found in 9.9% (P<0.001). An age-dependent quadratic trend was observed for multiple infections (P=0.01) with a trough at about 42 years. The most common HR-HPV types to show a coinfection with HPV16 (clade 9) were HPV39 (28%), 45 (38%), and 59 (46%), belonging to HPV18 clade 7. The frequency of low-risk (LR) vs probable HR and HR-HPV also followed an age-dependent quadratic trend.

Conclusions:

After the age of 25 years, HR-HPV prevalence is similar in LSIL and ASCUS cases, motivating a low age limit for triage HPV testing. Multiple infections and LR/HR-HPV dominance are age-dependent. Genotyping in longitudinal design is needed to elucidate the importance of multiple infections in cancer progression and in cross-protection from vaccination.     

Neurophysiological Markers for Monitoring Exercise and Recovery Cycles in Endurance Sports

The current study analyzes the suitability and reliability of selected neurophysiological and vegetative nervous system markers as biomarkers for exercise and recovery in endurance sport. Sixty-two healthy men and women, endurance trained and moderately trained, performed two identical acute endurance tests (running trial 1 and running trial 2) followed by a washout period of four weeks. Exercise protocol consisted of an acute running trial lasting 60 minutes. An intensity corresponding to 95% of the heart rate at individual anaerobic threshold for 40 minutes was followed by 20 minutes at 110%. At pre-exercise, post-exercise, three hours post-exercise and 24 hours post-exercise, experimental diagnostics on Brain-derived neurotrophic factor (BDNF), heart rate variability (HRV), Stroop Color and Word Test (SCWT), and Short-Form McGill Pain Questionnaire (SF-MPQ) were performed. Significant changes over time were found for all parameters (p < .05). Furthermore, there was an approached statistical significance in the interaction between gender and training status in BDNF regulation (F₍₃₎ = 2.43; p = 0.06), while gender differences were found only for LF/HF-ratio (3hPoEx, F₍₃₎ = 3.40; p = 0.002). Regarding the reliability, poor ICC-values (< 0.5) were found for BDNF, Stroop sensitivity and pNN50, while all other parameters showed moderate ICC-values (0.5-0.75). Plasma-BDNF, SCWT performance, pain perception and all HRV parameters are suitable exercise-sensitive markers after an acute endurance exercise. Moreover, pain perception, SCWT reaction time and all HRV parameters show a moderate reliability, others rather poor. In summary, a selected neurophysiological and vegetative marker panel can be used to determine exercise load and recovery in endurance sports, but its repeatability is limited due to its vaguely reliability. Key points

• Pain perception and the Stroop test have moderate reliability in the use of exercise and recovery markers after two identical exercise loads in endurance sports
• Markers of heart rate variability also show moderate reliability as biomarkers after intense endurance exercise under identical conditions.
• There are associations between neurophysiological markers and inflammatory blood markers after endurance exercise that are partially associated with gender and training status

Key words: NNervous system, monitoring training, biomarkers, reliability, executive function, heart rate variability     

Evaluation of Tableting and Tablet Properties of Kollidon SR: The Influence of Moisture and Mixtures with Theophylline Monohydrate

The aim of the study was firstly to investigate the influence of moisture on the tableting and tablet properties of Kollidon SR and secondly to investigate the influence of theophylline monohydrate on the tableting behavior and tablet properties produced from binary mixtures with Kollidon SR. In comparison to Kollidon SR, microcrystalline cellulose (MCC) was used. The glass transition temperature (T_g) of the powder over the whole range of RH (0–90%), and in addition, the T_g of tablets of Kollidon SR were measured. Densities and flowability of the powders were analyzed. The tablets were produced at five different maximum relative densities (ρ_{rel, max}) on an instrumented eccentric tableting machine. They were produced at three different relative humidities (RH), 30%, 45%, and 60% RH for the pure substances and binary mixtures with different ratios of drug and excipient were tableted at 45% RH. The tableting properties were analyzed by 3D modeling, force-displacement profiles, and compactibility plots. First, the T_g of the powder decreased with increasing RH and the T_g of the tablet was 4–8 K lower than the powder. The predominant deformation of Kollidon SR is plastic deformation and Kollidon SR showed a higher compactibility than MCC. The parameters of the 3D model showed an extreme change between 45 and 60% RH, and at higher RH more and more particles deformed elastically. This was confirmed by analysis of force-displacement profiles. At 60% RH, the radial tensile strength of the Kollidon SR tablets was half of the radial tensile strength at 45% RH. The reason is a higher relative energy of plastic deformation than for MCC. This results in a better utilization of the energy to deform the powder into a tablet and the exceeding of the glass transition temperature at higher RH. In conclusion, at 60% RH at the same ρ_{rel, max}, tableting and tablet properties of Kollidon SR are extremely changed since plasticity is significantly higher. In the second part of the study, the insufficient flowability of theophylline monohydrate can be compensated by using Kollidon SR in a mixture with up to 20% theophylline. Further, pressure plasticity ε of MCC and Kollidon SR was lowered in the mixture with theophylline monohydrate. The same is valid for the compactibility. The influence of theophylline monohydrate on the pressure plasticity e of the mixtures was better compensated in the mixture with MCC than in a mixture with Kollidon SR. This compensation was also visible by analyzing the force-displacement-profiles. However, hardly any influence on the radial tensile strength could be detected. Kollidon SR and Kollidon SR mixtures exhibited a higher compactibility than MCC and MCC mixtures. The differences became smaller with increasing theophylline content.