Chondrosarcoma in the Petrous Apex: Case Report and Review.

Introduction Surgical treatment of petrous apex chondrosarcoma is challenging due to the location of the tumor. Using an endoscopic technique for tumor resection is favored since it provides a minimally invasive approach. Case Presentation A 57 years old female was admitted for acute onset of left abducens nerve palsy and occasional headache mainly on the left side of the retro-orbital area with some radiation to the left occiput. Magnetic resonance imaging (MRI) and computed tomography (CT), at the time of admission, were showed lytic lesion on the left petrous apex and left part of the clivus. Results of metastatic workup were negative. The surgical procedure considered was expanded endoscopic endonasal transclival approach to the left of the petrous apex and reconstruction with a pedicled nasoseptal flap with image guidance system. The pathology confirmed chondrosarcoma on myxoid background. The surgical procedure was uncomplicated. The abducens nerve palsy was resolved in few weeks and no new deficits occurred. Postoperative MRI showed complete resection of the tumor. Conclusion Expanded endoscopic endonasal transclival approach to petrous apex and reconstruction appears to be safe and feasible technique, capable of achieving total removal of identified lesions near the petrous apex. Nonetheless, future studies with a greater number of patients are crucial to confirm and consolidate this initial impression.

Rear-side resonator architecture for the passive coherent combining of high-brightness laser diodes.

We describe a new coherent beam combining architecture based on passive phase locking of emitters in an extended cavity on the rear facet and their coherent combination on the front facet. This rear-side technique provides strong optical feedback for phase locking while maintaining a high electrical-to-optical efficiency. Two high-brightness high-power tapered laser diodes are coherently combined using a Michelson-based cavity. The combining efficiency is above 82% and results in an output power of 6.7 W in a nearly diffraction-limited beam with an M(4σ)(2)≤1.2. A semi-active automatic adjustment of the current enhances the long-term stability of the combination, while the short-term stability is passively ensured by the extended cavity. This new laser configuration exhibits the simplicity of passive self-organizing architectures while providing a power conversion efficiency of 27% that is comparable to master oscillator power amplifier architectures.

Abdominal Obesity and Type 2 Diabetes Mellitus are Associated With Higher Seric Levels of IL 4 in Adults.

AIMS: Study of IL4 in relation to the anthropometric, biochemical and immunological parameters in patients with obesity and/or diabetes. METHODS: The relationship between IL4 and clinical and biological parameters was studied in 76 patients divided into 4 groups: obese diabetics (OD), n = 25; obese without diabetes (O), n = 25; non obese diabetics (NOD), n = 11; controls (M), n = 15. IL4 was determined using the ELISA method. Statistical analysis was done using the MedCalc statistical software, version 16.1. RESULTS: Serum IL4 was 0.38 ±0,40 pg / mL in the Control group, 0.366 (0,100-2,35) pg / ml in group O, 4.66±3.73 pg / ml in group OD, 0.30 (0.10-1.35) pg / ml in NOD. When IL4 levels were compared between the four groups, statistical significance was reached for the comparison between groups OD and M. Statistically significant correlations were detected between IL4 and age, waist circumference and hip circumference, blood glucose, glycated hemoglobin (HbA1c), VLDL, triglycerides and serum protein fraction ß1. In univariate regression, the IL4 level predictors were age, height, BMI, abdominal circumference, hip circumference, beta 1% glucose, HbA1c, total lipids, total cholesterol, VLDL triglycerides, CRP. In multivariate regression, waist circumference and glycemia were significant predictors of levels of IL4 (p = 0.0001).

Pain and depression predict self-reported fatigue/energy in lupus.

UNLABELLED: This study examined the contribution of pain and psychological distress to fatigue. METHODS: One-hundred and twenty-five adult Caucasian and Hispanic lupus patients participated in this study. Demographic data, patient- and physician-reported disease activity, as well as psychological functioning, were collected. Fatigue, pain, and vitality were measured using visual analogue scales as well as a subscale of the SF-36 questionnaire. Linear and hierarchical regression analyses were conducted. In the regression analysis, ethnicity was entered at the first step, followed by age, income and education at step 2, pain and disease activity measures at step 3, and psychological measurements at step 4. RESULTS: In the linear regression analysis, Caucasians reported more fatigue. Fatigue positively correlated with income, education, pain, patient-reported disease activity, helplessness, and depression, and negatively with internality, and the energy analysis mirrored the results of the fatigue analysis. In the first regression analysis, fatigue was the dependent variable. At step 1, Caucasians reported more fatigue. At step 2, no other demographic variables were significant. At step 3, pain and disease activity measures were significant when entered as a block; however, pain independently explained a large amount of variance. At step 4, psychological factors were significant as a block, with depression being the strongest predictor. In the second analysis, energy was the dependent variable. At step 1, Hispanics reported more energy. At step 2, demographic variables were not significant. At step 3, pain and disease activity were significant when entered as a block; however, only pain uniquely predicted energy. At step 4, psychological factors were significant as a block, with depression as the major contributor. CONCLUSIONS: Both pain and depression were found to be strong predictors of fatigue, and negatively correlated with energy. Disease activity did not appear to play a significant role in lupus fatigue. These findings support the importance of managing depression and pain in order to reduce fatigue in patients with systemic lupus erythematosus.

Spanish LupusPRO: cross-cultural validation study for lupus.

PURPOSE: LupusPRO is a disease-targeted, patient-reported, outcome measure that was developed and validated among US patients with systemic lupus erythematosus (SLE). To expand the availability and use of the tool, we undertook a cross-cultural adaptation and validation study of the Spanish-translated version of the LupusPRO. METHOD: Forward and back translations of the 43-item English LupusPRO were undertaken and pretested in five individuals. The finalized Spanish version was administered to 211 SLE patients of Hispanic ancestry from the US and Latin America. Short Form-36 (Spanish) and Spanish LupusPRO were also administered. Disease activity was ascertained using the systemic lupus erythematosus disease activity index. A Spanish LupusPRO questionnaire that could be completed within 2-3 days was mailed to SLE patients of Hispanic ancestry and they mailed it back. Internal consistency reliability, test-retest reliability, criterion validity (against disease activity or health status) and convergent validity were tested. All reported p values are two-tailed. RESULTS: A total of 211 Spanish-speaking SLE patients (90% women) participated. Test-retest reliability of LupusPRO domains ranged from 0.80-0.95, while internal consistency reliability of the domains ranged from 0.71-0.96. Convergent validity with corresponding domains of the SF-36 was present. All health-related quality of life domains of the LupusPRO (except procreation) performed well against disease activity measures, establishing its criterion validity. Confirmatory factor analysis showed a good fit. CONCLUSION: The Spanish LupusPRO has fair psychometric properties and is now available to be included in clinical trials and in longitudinal studies for testing of responsiveness to change.

Successful nanolitre real-time PCR detection of respiratory pathogens in clinical specimens.

We performed a proof-of-concept study to determine if human pathogens could be detected in clinical specimens using nanolitre-volume real-time PCR. Nanolitre PCR for Bordetella pertussis/B. parapertussis and respiratory syncytial virus (RSV) was performed on nasopharyngeal specimens and results compared with conventional methods. B. pertussis/B. parapertussis nanolitre PCR detection was 100% sensitive (20/20; 95% CI, 84-100%) and 100% specific (26/26; 95% CI, 87-100%). RSV nanolitre PCR was also 100% sensitive (21/21; 95% CI, 85-100%) and specific (25/25; 95%, CI 87-100%). Respiratory pathogens can be successfully detected in clinical specimens using nanolitre-volume PCR.

The Patient Reported Outcomes in Lupus (PATROL) study: role of depression in health-related quality of life in a Southern California lupus cohort.

UNLABELLED: This study examines the relationship between psychosocial factors, ethnicity, disease activity and quality of life in systemic lupus erythematosus. METHODS: One hundred and twenty-five adult Caucasian and Hispanic lupus patients were recruited from four Southern California medical centers. Linear regression analysis was performed to assess the correlation of ethnicity, socioeconomic factors (age, income), and disease activity (patient and physician reported), as well as psychological (depression, internality, helplessness) variables with quality of life (QOL) as measured by the Short Form (SF)-36. Hierarchical multiple regression analysis was then used to determine the stepwise contribution of the above determinants on the eight domains of the SF-36 questionnaire. RESULTS: Depression negatively correlated with QOL in both Caucasians (r -0.488 to -0.660) and Hispanics (r -0.456 to -0.723). Patient-reported disease activity was moderately related (r -0.456 to -0.698) to seven of the eight SF-36 domains in Hispanics, and none in Caucasians. Physician-reported disease activity, measured by SLEDAI, did not correlate with QOL among Hispanics or Caucasians. When linear and hierarchical regression was used, depression significantly correlated (p < 0.0001) with the majority of the SF-36 domains, except general health, while age had a significant effect in only one domain of the SF-36, physical functioning (p < 0.0001). CONCLUSION: Depression, and not disease activity, appears to have a major influence on quality of life in both Hispanic and Caucasian patients in this lupus cohort.

Depression predicts self-reported disease activity in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease that can significantly impact both physiological and psychological functioning. In order to examine the relationship between psychological functioning and disease activity in SLE, we administered instruments that collected sociodemographic information and measured indices of disease activity and psychosocial functioning from 125 adult Hispanic and White patients with SLE. Patients were recruited from four healthcare settings in the greater Southern California area. Both cross-sectional and longitudinal relationships between depression and disease activity were evaluated. Cross-sectional findings revealed that depression and ethnicity were independently correlated with self-reported disease activity. Longitudinally, depression alone predicted self-reported disease activity. These data suggest that depression may play a significant role in the health status of SLE patients and serve as an important target for clinical intervention.

[New morpho-functional rehabilitation methods in cleft lip and palate]. / Noi metode de reabilitare morfo-functionala în despicaturile labio-maxilo-palatine.

UNLABELLED: The interdisciplinary, complex therapeutic protocol of the cleft lip and palate patients, applied in the Clinic of Cranio-Maxillo-Facial Surgery of "I. Hatieganu" University of Medicine and Pharmacy Cluj-Napoca, involves the morphologic reconstruction as well as the functional rehabilitation. Functional rehabilitation is the aspect, which gives the esthetics, social and familial integration of the patient, offering good quality of life. METHOD: In the current study, a new method and concept of improving the phonetic function in the primary and secondary surgical steps, with the effect on muscle and bone, is presented. The new surgical techniques used comprise of the surgery of the levator veli palatini using the method designed by Sader, and bone distraction, during the same surgical procedure. The assessment of the phonetic results was performed using the NARSOM test. RESULTS: Following up the results of the techniques mentioned above, we consider that they improve extremely well the morphological status, while giving a functional and physiological support to the patient. CONCLUSION: Thus, they offer optimal conditions for the future progress of functional rehabilitation using specific speech therapy methods.

Longitudinal single-cell cytokine responses reveal recurrent autoimmune myelin reactivity in relapsing--remitting multiple sclerosis patients.

The relationship between multiple sclerosis (MS) disease activity and myelin protein-induced cytokine responses over time is not elucidated. We addressed this relationship by examining longitudinal cytokine responses to myelin proteins every three months for one year, in the context of gadolinium (gad)-enhancing brain lesions and of clinical relapses. The ELISPOT assay was used to determine the ex vivo cytokine production in response to nine amino acid long peptides spanning the entire proteolipid protein (PLP) and myelin basic protein (MBP) molecules in relapsing-remitting (RR) MS patients and matched healthy controls. We identified three longitudinal levels of myelin-induced cytokine secretion by adding up the positive responses for all PLP or MBP peptides obtained for five timepoints, at three-month intervals: low reactivity (< 200 cumulative cytokine-secreting cells), isolated peptide reactivity (201-450 cumulative cytokine-secreting cells) and recurrent protein-wide bursts of cytokine reactivity (> 451 cumulative cytokine-secreting cells). The majority of MS patients showed recurrent bursts to PLP and MBP. In contrast, controls showed a more even distribution between all levels of cytokine reactivity. The majority of patients with gad-enhancing lesions showed PLP/IFN gamma and MBP/IFN gamma recurrent burst responses. This is the first longitudinal study on MS patients in which nine amino acid long myelin peptides are used to reveal the broad range of PLP- and MBP-peptide cytokine reactivity across the whole molecule of these two major myelin proteins. This study also reveals the extremely dynamic nature of the immune reactivity to numerous regions of myelin, which can fluctuate dramatically over time. Such fluctuation could hamper the efficacy of antigen-based therapies for MS.

Interaction of human immunoglobulin G with CD16 on natural killer cells: ligand clearance, FcgammaRIIIA turnover and effects of metalloproteinases on FcgammaRIIIA-mediated binding, signal transduction and killing.

Human natural killer (NK) cells express low-affinity Fc immunoglobulin G (IgG) receptor (FcgammaRIIIA/CD16). The binding of monomeric IgG (mIgG) and F(ab')(2) fragments of 3G8 anti-CD16 monoclonal antibody (mAb) to FcgammaRIIIA was investigated by flow cytometry. Over 90% of NK cells bound endogenous IgG, and during incubation at 37 degrees C, the FcgammaRIIIA occupancy decreased slowly. Approximately 90% of NK cells bind mIgG or F(ab')(2) fragments of 3G8 anti-CD16 mAb. The calculated half-time (T(1/2)) of in vitro mIgG dissociation from FcgammaRIIIA was 130 min. By cross-linking the mIgG ligand with F(ab')(2) fragments of anti-human IgG antibody, the T(1/2) decreases to 85 min. In kinetics study, it has been shown that (125)I-mIgG bound to FcgammaRIIIA is slowly released in the culture supernatant, maybe eluted at acid pH, or partially internalized and degraded. The binding of IgG to FcgammaRIIIA was increased by 53.8% on cells cultured in the presence of RU36156, a matrix metalloproteinase (MMP) inhibitor. Furthermore, an increase in phosphorylation of Lyn tyrosine kinase, after cross-linking of mIgG-FcgammaRIIIA complex, was observed on NK cells treated with RU36156. When the FcgammaRIIIA was occupied by mIgG, the capacity of NK cells to kill K562 target cells was decreased by RU36156, because the MMP inhibitor protects CD16 from proteolysis. Our data demonstrate that binding of mIgG to human NK cells is followed by ligand dissociation and/or internalization, enzymatic degradation and exocytosis. The RU36156 MMP inhibitor protects FcgammaRIIIA from cleavage, augments NK-cell activation and may interfere in their killing capacity.

Regulation of production of soluble Fc gamma receptors type III in normal and pathological conditions.

CD16 (Fc gamma R type III), a low affinity IgG Fc receptor, is found in two forms, a transmembrane Fc gamma RIIIa expressed by NK cells and monocytes and a phosphatidylinositol-linked Fc gamma RIIIb present on neutrophils. Exposure of neutrophils to inflammatory signals induces a rapid loss of CD16 expression and release of a soluble form of CD16 (sCD16). Soluble CD16 circulates in plasma, levels being reduced in sera from patients with multiple myeloma. In the present manuscript the authors summarize work that aimed to better understand: (i) the role of proteinases in sCD16 production and CD16 membrane shedding; and (ii) the regulation of sCD16 levels in multiple myeloma patients and the possible biological consequences of its decrease in this disease. Soluble CD16 was purified from human serum. Its N-terminal sequencing demonstrated that it originates from neutrophil CD16 and its C-terminal sequencing showed that the cleavage site was between Val 196 and Ser 197, close to the membrane anchor. Analysis of the effect of protease inhibitors revealed that the cleavage leading to sCD16 production by PMA-activated neutrophils was metalloproteinase-dependent. In addition, membrane and sCD16 were sensitive to serine proteinases released by azurophil granules or added under purified form. The reduction of sCD16 levels that occurs in patients with multiple myeloma was associated with a slight decrease in circulating neutrophils, but not with a significant defect in sCD16 production by neutrophils, as detected in vitro. Moreover, addition of a recombinant sCD16 to plasmocytoma lines did not significantly modify their proliferation and Ig secretion.

Evaluation of apoptosis of tumor and of apparently normal cells in human renal carcinoma.

Apoptosis of tumor cells and of apparently normal renal cells (ANRC) isolated from the same kidney in 42 untreated patients with renal carcinomas (RC) was evaluated. Thirty five of the investigated tumors were of Grawitz type in different grades of differentiation. The intensity of the apoptotic process was routinely assessed by propidium iodide staining and flow-cytometry analysis. Similar results were obtained in the same cases by using TUNEL assay, by staining with annexin V and by DNA electrophoresis. In 85% of Grawitz carcinomas the proportion of apoptotic tumor cells was quite high, with mean% +/- SD of 57.7+/-27.3, whereas in transitional cell carcinoma of the bladder (TCC), the mean percentage of cells in apoptosis was of 22.3+/-13.9. Unexpectedly, in ANRC displaying normal morphology and normal DNA content (diploidy), the mean% +/- SD of apoptotic cells were found to exceed that of apoptotic tumor cells, 79.2+/-21.6. The percentages of cells expressing Fas receptor and/or Fas ligand varied between large ranges in both tumor and ANRC, thus suggesting that other mechanisms are also involved in the activation of apoptosis. Immunohistochemical studies showed that the intensity of apoptosis correlated well with high p-53 and low bcl-2 expression. The intensity of apoptosis was generally not correlated with the cell proliferation index (S phase fraction), suggesting that in RC apoptosis can be activated in any stage of the cell cycle. Further investigations are necessary to understand the peculiar behaviour of tumor cells as well as of ANRC in renal carcinomas as compared to other types of malignancies.

Identification of the cleavage site involved in production of plasma soluble Fc gamma receptor type III (CD16).

CD16 (FcgammaR type III) is a low-affinity IgG Fc receptor (R) that exists in two isoforms, a transmembrane FcgammaRIIIa expressed by NK cells and monocytes, and a phosphatidylinositol-linked FcgammaRIIIb expressed by neutrophils. A soluble form of CD16 (sCD16) circulates in plasma. The cleavage site and the nature of the enzyme(s) involved in production of sCD16 were investigated. Soluble CD16 was purified to apparent homogeneity from human serum by eight steps, including anion exchange and immunoaffinity chromatography. Serum sCD16 was sequenced at both ends, as well as a recombinant form of sCD16 used as control. N-terminal sequencing demonstrated that serum sCD16 originates from neutrophil FcgammaRIIIb and C-terminal sequencing suggested that the cleavage site is between Val 196 and Ser 197, close to the membrane anchor. Addition of a hydroxamate-based inhibitor of Zn2+ metalloproteinases (RU36156) led to a dramatic decrease of sCD16 production by phorbol 12-myristate 13-acetate-activated neutrophils, whereas inhibitors of serine proteinases had no significant effect, showing the metalloproteinase dependence of this cleavage process.

Lymphocyte subset reference ranges in Romanian adult Caucasians.

The paper reports the distribution of lymphocyte subpopulations in the Caucasian population of Romania. Investigations were carried out in cells bearing the following antigens: CD3 (T cells), CD19 (B cells), CD4 (T helper/inducer cells), CD8 (T suppressor/cytotoxic and some NK cells), and CD16 CD56 (NK cells). Reference values for the lymphocyte subpopulation were obtained from over 100 healthy Caucasian adult volunteers. Blood from these donors was analyzed using FACScan flow cytometer, Leuco-GATE, Simultest and FACS Lysing Solution, and SimulSET software. As an internal quality control, it was verified that %T+%B+%NK approximates 100% in all samples. The results presented here, obtained on healthy donors (51 males and 49 females), showed that there are no statistically significant variations of CD4/CD8 ratio related to sex or age, the mean value of this ratio (2.0 +/- 0.02) being similar to that reported by the West-European countries. Additional similarities were found when the relative percentage, mean +/- standard deviation (CD3 = 74.2 +/- 2.8; CD19 = 10.8 +/- 1.6; CD4 = 42.0 +/- 2.5; CD8 = 28.9 +/- 5.7; CD56 = 15.2 +/- 0.4) and the absolute cell number of the major peripheral blood mononuclear subsets established in our study were compared with other published results. This study was entirely supported by Becton Dickinson--Europe (Division Heidelberg, Germany).

Expression and function of Fc gamma RII on human natural killer cells.

In this report, we present data on the expression and function of Fc gamma RII (CD32) by natural killer (NK) cells. Highly enriched NK cell populations were isolated from peripheral blood lymphocytes by negative selection and consisted of > or = 95% CD3-/CD56+ cells. Flow cytometric analyses with anti-CD32 monoclonal antibodies (mAbs) demonstrated that a small proportion of NK cells were recognized by mAbs IV.3 and 41H16. Two-color flow cytometric analysis indicated coexpression of the epitope on NK cells recognized by both these mAbs. Verification of expression of CD32 on NK cells was obtained by demonstrating coexpression of CD32 on either CD16+ or CD56+ cells. The CD32+/CD16+ and CD32+/CD56+ cells represented approximately 7 and 3% of the total, respectively. CD32 transcripts were identified from highly purified NK cells using reverse transcription-polymerase chain reaction with CD32-specific primers, followed by Southern blotting. Enhanced chemiluminescence-Western blot (ECL-WB) analysis of lysates of purified NK cells indicated that mAb IV.3 recognized a molecule of approximately 40 kD. The Fc gamma RII on NK cells was able to transduce intracellular signals in several types of assay. Cross-linking of anti-CD32 resulted in a mobilization of intracellular Ca2+, although to a lesser extent than that induced by cross-linking CD16. Both mAbs IV.3 and 41H16 were found to be capable of inducing reverse antibody-dependent cellular cytotoxicity against FcR+ target cells (e.g. P815). These data represent the first direct description of the expression and function of Fc gamma RII on human NK cells.

[Control of the metabolic state of diabetic patients by determining the concentration of serum glycosylated proteins (the fructosamine test)]. / Controlul starii metabolice a bolnavilor cu diabet zaharat prin determinarea concentratiei proteinelor serice glicozilate (testul "fructozaminei").

The method for determining glycosylate serum proteins is based on the ketoamines property (fructosamine) of reducing nitro-tetrazoline blue, in alkaline medium, to a coloured, photometric product. The technique is simple, rapid, reproducible and cheap. The method was used for investigation of 52 diabetics and 17 normal subjects. The normal values were between 1.50-2.70 mmol/l, uncertain between 2.70-3.00 mmol/l, and certainly pathological above 3.00 mmol/l. The level of serum fructosamines shows the glycemia variations for an average period of about two weeks, before determination. It is one of the valuable parameters for detecting and following the patients with diabetes mellitus, and has also a prognostic value in the evolution of the disease.

Fibronectin and phagocytosis in acute and chronic infections.

Serum fibronectin (Fn) level and phagocytosis function were investigated during acute and chronic infections. Serum Fn concentration was significantly decreased in septic patients (mean +/- ES, 80 +/- 12 micrograms/ml, p less than 0.001) and was increased in chronic bronchitis patients (575 +/- 18 micrograms/ml, p less than 0.001) as compared to the controls. The phagocytosis index was decreased in septicaemia and not significantly changed in chronic bronchitis. Phagocytosis dysfunction was associated to a low serum Fn level in acute infections. Phagocytosis was stimulated in vitro, by purified Fn. Serum Fn concentration reflects the reticuloendothelial function and could be a marker of infection together with other parameters.