Observations on intraoperative somatosensory evoked potential (SEP) monitoring in the semi-sitting position.

BACKGROUND: Former case reports suggest that monitoring of median nerve somatosensory evoked potentials (M-SEP) is unreliable in patients operated in the semi-sitting position due to the occurrence of evoked potential changes unrelated to neurological damage. This study was designed to analyze these changes in greater detail and confirm that these changes are not caused by neurological damage. METHODS: M-SEP monitoring findings of 50 patients with surgery in the semi-sitting position were analyzed and compared with a group of 50 patients who underwent surgery in the supine position. M-SEP amplitudes and latencies at distinct steps of the monitoring procedure were used for further analysis. In 10 of the 50 semi-sitting patients, M-SEP were recorded additionally after surgery with the anesthetized patient in the supine position. RESULTS: Significant M-SEP changes occurred in the semi-sitting patients only. An amplitude loss of greater than 50% on at least one side was observed in 24 patients. The magnitude and the time course of the amplitude loss was considerably variable. A complete loss of the evoked potential was not observed in any case. In all 10 patients, M-SEP recovered completely when recorded in the supine position. CONCLUSIONS: In about half of the patients with M-SEP monitoring in the semi-sitting position, a significant amplitude loss occurs which is unrelated to neurological damage and presumably caused by subdural gas collections. There is no characteristic pattern of M-SEP changes which enables a differentiation of these 'artificial' alterations from true events. The only appropriate criterion to indicate an impending neurological damage in these patients seems to be a complete loss of the M-SEP potential.     

How Unusual are the Contents of Paraphilias? Paraphilia-Associated Sexual Arousal Patterns in a Community-Based Sample of Men

IntroductionThis is a report of a cross-sectional study on paraphilia-associated sexual arousal patterns (PASAP) among men in a metropolitan city in Germany, EU.AimTo determine the prevalence of PASAP during sexual fantasies, fantasies accompanying masturbation, and real-life sociosexual behavior.MethodsIn a cross-sectional study, self-reported sexual history data were collected by questionnaire from 367 volunteers recruited from a community sample of 1,915 men aged 40–79 years.Main Outcome MeasuresThe Derogatis Symptom Checklist—Revised (SCL-90–R) and the Life Satisfaction Questionnaire (LSQ; German original, Fragebogen zur Lebenszufriedenheit, [FLZ]) were administered to obtain a general subjective health measure and a measure of general as well as sex life satisfaction. The Questionnaire on Sexual Experiences and Behaviour was administered to comprehensively assess all relevant sexo-medical data.ResultsThe percent of men that reported at least one PASAP was 62.4%. In 1.7% of cases, PASAP were reported to have caused distress. The presence of PASAP was associated with a higher likelihood of being single (odds ratio [OR] 2.6; 95%; confidence interval [CI] 1.047–6.640), masturbating at least once per week (OR 4.4; 95%; CI 1.773–10.914), or having a low general subjective health score (OR 11.9; 95%; CI 2.601–54.553). Pedophilic PASAP in sexual fantasies and in real-life sociosexual behavior was reported by 9.5% and 3.8% of participants, respectively.ConclusionThe findings suggest that paraphilia-related experience can not be regarded as unusual from a normative perspective. At the same time, many men experience PASAP without accompanying problem awareness or distress, even when PASAP contents are associated with potentially causing harm to others. In view of the relevance for sex life and relationship satisfaction, presence of PASAP should be assessed in all sexual medicine consultations. Future research should focus on conditions in which PASAP reach clinical significance in the sense of mental disorders. Ahlers CJ, Schaefer GA, Mundt IA, Roll S, Englert H, Willich SN, and Beier KM. How unusual are the contents of paraphilias? Paraphilia-associated sexual arousal patterns in a community-based sample of men.     

Characterization of the sensitizing potential of chemicals by in vitro analysis of dendritic cell activation and skin penetration

Development of in vitro models to identify sensitizing chemicals receives public interest since animal testing should be avoided whenever possible. In this article we analyze two essential properties of sensitizing chemicals: skin penetration and dendritic cell (DC) activation. Activation of immature DC derived from peripheral blood monocytes was evaluated by flow cytometric analysis of CD86 positive cells and quantitative measurement of interleukin-1beta and aquaporin P3 gene expression. The sensitizer 2,4,6-trinitrobenzenesulfonic acid induced a concentration-dependent response for all parameters, whereas the irritant sodium lauryl sulfate did not. When two related aromatic amines, p-toluylenediamine (PTD) and hydroxyethyl-p-phenylenediamine (HE-PPD) were tested, both induced substantial DC activation indicating their potential sensitizing properties. These findings contrasted with in vivo results: in murine local lymph node assays (LLNA) PTD, but not HE-PPD, was sensitizing using acetone/aqua/olive oil as vehicle. Skin penetration measurement revealed that this was due to bioavailability differences. On retesting HE-PPD in the LLNA using the penetration enhancer dimethylsulfoxide as vehicle, it induced a specific response. We conclude that in vitro analysis of DC activation capability of the two selected chemicals demonstrates that prediction of skin sensitization potential is possible provided that skin penetration data indicate sufficient bioavailability of the test compound.     

Stroma formation and angiogenesis by overexpression of growth factors,cytokines, and proteolytic enzymes in human skin grafted to SCID mice

Reorganization of skin during wound healing, inflammatory disorders, or cancer growth is the result of expression changes of multiple genes associated with tissue morphogenesis. We wanted to identify proteins involved in skin remodeling and select those that may be targeted for agonistic or antagonist therapeutic approaches in various disease processes. Full-thickness human skin was grafted to severe combined immunodeficient mice and injected intradermally with 38 different adenoviral vectors inserted with 37 different genes coding for growth factors, cytokines, proteolytic enzymes and their inhibitors, adhesion receptors, oncogenes, and tumor suppressor genes. Responses were characterized for infiltration of inflammatory cells, vascular density, matrix formation, fibroblast-like cell proliferation, and epidermal hyperplasia. Of the 17 growth factor vectors, 16 induced histological changes in human skin. Members of the VEGF and angiopoietin families induced neovascularization. PDGFs and TGF-betas stimulated connective tissue formation, and the chemokines IL-8 and MCP-1 attracted inflammatory neutrophils and monocytes, respectively. The serine protease uPA induced a vascular response similar to that of VEGF. Vectors with adhesion receptors, oncogenes and tumor suppressor genes had, with few exceptions, little effects on skin architecture. The overall results suggest that adenoviral vectors can effectively remodel the architecture of human skin for studies in morphogenesis, inflammatory skin disorders, wound healing, and cancer development.     

Expression and localization of peroxisome proliferator-activated receptors and nuclear factor kappaB in normal and lesional psoriatic skin

Abnormal epidermal proliferation and differentiation characterize the inflammatory skin disease psoriasis. Here we demonstrate that expression of PPARdelta mRNA and protein is markedly upregulated in psoriatic lesions and that lipoxygenase products accumulating in psoriatic lesions are potent activators of PPARdelta. The expression levels of NF-kappaB p50 and p65 were not significantly altered in lesional compared with nonlesional psoriatic skin. In the basal layer of normal epidermis both p50 and p65 were sequestered in the cytoplasm, whereas p50, but not p65, localized to nuclei in the suprabasal layers, and this distribution was maintained in lesional psoriatic skin. In normal human keratinocytes PPAR agonists neither impaired IL-1beta-induced translocation of p65 nor IL-1beta-induced NF-kappaB DNA binding. We show that PPARdelta physically interacts with the N-terminal Rel homology domain of p65. Irrespective of the presence of agonists none of the PPAR subtypes decreased p65-mediated transactivation in keratinocytes. In contrast p65, but not p50, was a potent repressor of PPAR-mediated transactivation. The p65-dependent repression of PPARdelta- but not PPARalpha- or PPARgamma-mediated transactivation was partially relieved by forced expression of the coactivators p300 or CBP. We suggest that deficient NF-kappaB activation in chronic psoriatic plaques permitting unabated PPARdelta-mediated transactivation contributes to the pathologic phenotype of psoriasis.     

Diagnostic odyssey of a cutaneous mycobacteriosis rare in central Europe

Cutaneous infection with Mycobacterium chelonae is an uncommon disease, although this atypical mycobacterium is an acid-fast bacillus ubiquitous in the environment. It is often misdiagnosed and treated as a fungal or common bacterial infection. We report a case of disseminated atypical mycobacterial skin infection of a 72-year-old woman who was treated with different topical and systemic antimycotic and antibiotic drugs over a period of 5 months without remarkable improvement. Eventually, repeated tissue cultures on special medium and performance of PCR led to the diagnosis of M. chelonae infection. The patient was treated successfully with oral clarithromycin within 8 weeks. In case of abscessing cutaneous infection, M. chelonae should be considered in the differential diagnosis of prolonged disease when common antibiotics are not effective after 2-4 weeks of treatment.     

Three-year follow-up of high-risk keratoplasty following fine-needle diathermy of corneal neovascularization combined with bevacizumab

Graefe's Archive for Clinical and Experimental Ophthalmology -     

Autonomic information flow improves prognostic value of heart rate patterns after abdominal aortic surgery

PURPOSE: Complex autonomic communication can be assessed by autonomic information flow (AIF) functions. The objective was to evaluate new complexity measures involving physiologically relevant time scales to predict the length of stay (LOS) in the hospital after abdominal aortic surgery (AAS). Our hypothesis was that AAS disrupts AIF, that restoration of AIF is necessary for recovery from major surgery, and that measures of AIF are superior to conventional heart rate variability (HRV) measures and equivalent to APACHE IV score in predicting LOS. MATERIALS AND METHODS: Twenty-four-hour Holter recordings were analyzed in 94 patients after AAS for standard time, frequency domain, and several complexity measures of different time scales derived from AIF functions. The risk of staying in the hospital for longer than 7 days as a function of HRV measures and APACHE IV score was modeled by logistic regression. The area under the curve (AUC) of receiver operating characteristic with 95% confidence interval as measure of predictive accuracy was calculated and internally cross-validated. RESULTS: The long-term decay of AIF over 100s (LD100) with cross-validated AUC = 0.67 (0.56-0.79) nearly reached the predictive accuracy of the APACHE IV score with AUC = 0.69 (0.58-0.79). None of the traditional time and frequency domain HRV measures remained in the multivariate models. The LD100 adjusted for ventilatory support with AUC = 0.70 (0.59-0.81) was equivalent to the APACHE IV score in this patient group. Although the strongest correlation between AIF measures and the APACHE IV score was found for LD100, r was only -0.37. CONCLUSIONS: Results confirm the hypothesis that AIF measures characterize pathophysiologic autonomic communication better than traditional HRV measures and may have similar predictive value to the APACHE IV score for LOS. The relative independence of the APACHE IV score and AIF measures suggests that AIF measures could add to clinical risk prediction.     

Childhood traumatic grief: a multi-site empirical examination of the construct and its correlates

This study evaluated the construct of childhood traumatic grief (CTG) and its correlates through a multi-site assessment of 132 bereaved children and adolescents. Youth completed a new measure of the characteristics, attributions, and reactions to exposure to death (CARED), as well as measures of CTG, posttraumatic stress disorder (PTSD), depression, and anger. CTG was distinct from but highly correlated with PTSD, depression, and, to a lesser degree, anger. In contrast to a recent study of complicated grief, CTG severity was significantly associated with the degree to which the death was viewed as traumatic. CTG was also associated with caregivers' emotional reaction at the time of the death and caregivers' current sadness. Clinical implications and recommendations for future research are discussed.     

Phase 1 evaluation of intralesionally injected TLR9-agonist PF-3512676 in patients with basal cell carcinoma or metastatic melanoma

Synthetic oligodeoxynucleotides (ODNs), such as PF-3512676, that contain unmethylated cytosine-guanine motifs (CpG ODN) have been identified as highly potent immune activators by in vitro examinations and in murine models. CpG ODNs induce innate and adaptive immune responses by triggering Toll-like receptor 9 expressed by human B cells and plasmacytoid dendritic cells. A phase 1 study was initiated to investigate safety, tolerability, serum cytokine levels, cellular immune responses, and clinical activity of intralesional treatment with PF-3512676 in patients with basal cell carcinoma (BCC) or cutaneous or subcutaneous melanoma metastases. Intrapatient escalating doses of PF-3512676 (up to 10 mg) were injected intralesionally every 14 days in 5 patients with BCC and in cutaneous or subcutaneous metastases of 5 patients with melanoma. PF-3512676 was well tolerated. Local swelling and erythema occurred at the injection site in 9/10 patients. There was only 1 incidence of a grade III hematologic adverse event (lymphocytopenia). Local tumor regressions were observed in patients with BCC (1 complete regression, 4 partial regressions) and metastatic melanoma (1 complete regression). After treatment with PF-3512676, interleukin-6 was increased in all patients, interferon-gamma induced protein-10 in 8/10 patients, interleukin-12p40 in 7/10 patients, and tumor necrosis factor-alpha levels in 6/10 patients. All patients had biopsies; moderate to abundant cellular infiltrates of lymphocytes were found posttreatment in most lesions of both histologic types. Intralesional treatment of skin tumors with PF-3512676 was safe and well tolerated. Despite the relatively low dosage, clinical activity was demonstrated both in patients with BCC and with cutaneous or subcutaneous metastatic melanoma lesions.