T2* and quantitative susceptibility mapping in an equine model of post-traumatic osteoarthritis: assessment of mechanical and structural properties of articular cartilage.

OBJECTIVE: To investigate the potential of quantitative susceptibility mapping (QSM) and T2* relaxation time mapping to determine mechanical and structural properties of articular cartilage via univariate and multivariate analysis. METHODS: Samples were obtained from a cartilage repair study, in which surgically induced full-thickness chondral defects in the stifle joints of seven Shetland ponies caused post-traumatic osteoarthritis (14 samples). Control samples were collected from non-operated joints of three animals (6 samples). Magnetic resonance imaging (MRI) was performed at 9.4 T, using a 3-D multi-echo gradient echo sequence. Biomechanical testing, digital densitometry (DD) and polarized light microscopy (PLM) were utilized as reference methods. To compare MRI parameters with reference parameters (equilibrium and dynamic moduli, proteoglycan content, collagen fiber angle and -anisotropy), depth-wise profiles of MRI parameters were acquired at the biomechanical testing locations. Partial least squares regression (PLSR) and Spearman's rank correlation were utilized in data analysis. RESULTS: PLSR indicated a moderate-to-strong correlation (ρ = 0.49-0.66) and a moderate correlation (ρ = 0.41-0.55) between the reference values and T2* relaxation time and QSM profiles, respectively (excluding superficial-only results). PLSR correlations were noticeably higher than direct correlations between bulk MRI and reference parameters. 3-D parametric surface maps revealed spatial variations in the MRI parameters between experimental and control groups. CONCLUSION: Quantitative parameters from 3-D multi-echo gradient echo MRI can be utilized to predict the properties of articular cartilage. With PLSR, especially the T2* relaxation time profile appeared to correlate with the properties of cartilage. Furthermore, the results suggest that degeneration affects the QSM-contrast in the cartilage. However, this change in contrast is not easy to quantify.

[A BANEFUL CUTANEOUS LESION]. / Un placard cutané funeste.

We report the case of a patient presenting meningeal carcinomatosis and cutanenous metastasis as first manifestation of gastric adenocarcinoma. A 57-year-old patient was hospitalized because of headache and diplopia. Clinical examination revealed VI cranial nerve paralysis and anterior neck infiltration. Cutaneous biopsy and umbar puncture showed signet ring-cells. Extensive work-up disclosed gastric adenocarcinoma. Cutaneous metastasis and carcinomatous metastasis are both present exceptionally as first manifestation of gastric adenocarcinoma. We discuss frequency, etiology and treatment of these manifestations.

Metabolite profile of marine-derived endophytic Streptomyces sundarbansensis WR1L1S8 by liquid chromatography-mass spectrometry and evaluation of culture conditions on antibacterial activity and mycelial growth.

AIMS: This study was designed to investigate whether culture conditions (media, seawater concentration and pH) could lead Streptomyces sundarbansensis strain (isolated from marine brown algae Fucus sp. collected from Algerian coastline) to produce bioactive secondary metabolites. The most favourable condition for the production of anti-MRSA compound 1 [2-hydroxy-5-((6-hydroxy-4-oxo-4H-pyran-2-yl)methyl)-2-propylchroman-4-one] was determined. METHODS AND RESULTS: The profile of metabolites present in the crude extracts was carried out by HPLC analysis equipped with a diode array detector evaporative light scattering detection (DAD-ELSD) or online coupled to electrospray ionization-mass spectrometry (ESI-MS). Compound 1 was the most abundant secondary metabolite by culturing the strains on starch casein agar (SCA) medium in freshwater or 50% seawater at pH 7 or 9 using agar-state fermentation method. CONCLUSIONS: The study has shown the efficiency of HPLC/ESI-MS technique in the analysis of polyketides produced by the strain under investigation. It was possible to establish the best culture conditions for obtaining the most bioactive compound 1, previously isolated by the same strain. SIGNIFICANCE AND IMPACT OF THE STUDY: Marine algae-actinobacteria associations are a particularly promising renewable system for the production of new antibacterial metabolites. Based on the promising bioactivity of the chemically characterized compound 1, the analytical methodology here applied has resulted as an effective approach for establishing its optimized production.

Infrared spectroscopy of copper-resveratrol complexes: a joint experimental and theoretical study.

Infrared multiple-photon dissociation spectroscopy has been used to record vibrational spectra of charged copper-resveratrol complexes in the 3500-3700 cm(-1) and 1100-1900 cm(-1) regions. Minimum energy structures have been determined by density functional theory calculations using plane waves and pseudopotentials. In particular, the copper(I)-resveratrol complex presents a tetra-coordinated metal bound with two carbon atoms of the alkenyl moiety and two closest carbons of the adjoining resorcinol ring. For these geometries vibrational spectra have been calculated by using linear response theory. The good agreement between experimental and calculated IR spectra for the selected species confirms the overall reliability of the proposed geometries.

Lombardy diagnostic and therapeutic network of thrombotic microangiopathy.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening thrombotic microangiopathy (TMA) requiring urgent treatment. Standardization of its diagnosis and optimal management is challenging. This study aimed to evaluate the role of centralized, rapid testing of ADAMTS13 in patients experiencing acute TMAs requiring plasma-exchange (PEX) and to estimate the incidence of TTP in a large Italian Region. METHODS: We perfomed a cohort study in the frame of the project "Set-up of a Lombardy network for the study and treatment of patients undergoing apheresis", including 11 transfusion centers in the Region. Consecutive patients referred from 2014 to 2016 with acute TMAs requiring PEX were enrolled. Centralized ADAMTS13 activity testing was performed at the Milan Hemophilia and Thrombosis Center within 24 h. RESULTS: Forty-three TMA patients (44 events) were enrolled, of whom 35 (81%) had severe ADAMTS13 deficiency. Patients with severe ADAMTS13 deficiency were younger, mainly women, with a higher prevalence of autoimmune disorders and a lower prevalence of cancer. Clinical and laboratory characteristics of patients with and without severe ADAMTS13 deficiency largely overlapped, with a lower platelet count being the only baseline marker that significantly differed between the two patient groups (ADAMTS13 activity < 10% vs ≥ 10%: median difference of -27 × 109/l, 95% CI - 37 to - 3). PEX treatment was initiated in all patients, but soon discontinued in cases without severe ADAMTS13 deficiency. In this group, the mortality rate was higher and no episode exacerbations or relapses within 6 months occured. The estimated average annual incidence of acute acquired TTP events was 1.17 [0.78-1.55] per million people. CONCLUSIONS: Severe ADAMTS13 deficiency distinguished two groups of patients with largely overlapping clinical features but different treatment and disease course. This study provides a feasible model implemented in a large Italian region for the practical clinical approach to TMAs and underlines the importance of urgent ADAMTS13 activity testing for an accurate differential diagnosis and therapeutic approach.

A composite hydrogel-3D printed thermoplast osteochondral anchor as example for a zonal approach to cartilage repair: in vivo performance in a long-term equine model.

Recent research has been focusing on the generation of living personalized osteochondral constructs for joint repair. Native articular cartilage has a zonal structure, which is not reflected in current constructs and which may be a cause of the frequent failure of these repair attempts. Therefore, we investigated the performance of a composite implant that further reflects the zonal distribution of cellular component both in vitro and in vivo in a long-term equine model. Constructs constituted of a 3D-printed poly(ϵ-caprolactone) (PCL) bone anchor from which reinforcing fibers protruded into the chondral part of the construct over which two layers of a thiol-ene cross-linkable hyaluronic acid/poly(glycidol) hybrid hydrogel (HA-SH/P(AGE-co-G)) were fabricated. The top layer contained Articular Cartilage Progenitor Cells (ACPCs) derived from the superficial layer of native cartilage tissue, the bottom layer contained mesenchymal stromal cells (MSCs). The chondral part of control constructs were homogeneously filled with MSCs. After six months in vivo, microtomography revealed significant bone growth into the anchor. Histologically, there was only limited production of cartilage-like tissue (despite persistency of hydrogel) both in zonal and non-zonal constructs. There were no differences in histological scoring; however, the repair tissue was significantly stiffer in defects repaired with zonal constructs. The sub-optimal quality of the repair tissue may be related to several factors, including early loss of implanted cells, or inappropriate degradation rate of the hydrogel. Nonetheless, this approach may be promising and research into further tailoring of biomaterials and of construct characteristics seems warranted.

CO2 and N2O from water resource recovery facilities: Evaluation of emissions from biological treatment, settling, disinfection, and receiving water body.

Water resource recovery facilities (WRRFs) contribute to climate change and air pollution, as they are anthropogenic potential sources of direct and indirect emission of greenhouse gases (GHGs). Studies concerning the monitoring and accounting for GHG emissions from WRRFs are of increasing interest. In this study, the floating hood technique for gas collection was coupled with the off-gas method to monitor and apportion nitrous oxide (N2O) and carbon dioxide (CO2) emissions from both aerated and non-aerated tanks in a municipal water resource recovery facility, in order to investigate its carbon footprint (CFP). To our knowledge, this is the first time that the chamber technique was applied to evaluate gas fluxes from the settler, where an emission factor (EF) of 4.71 ∗ 10-5 kgCO2,eq kgbCOD-1 was found. Interesting results were found in the disinfection unit, which was the major contributor to direct N2O emissions (with a specific emission factor of 0.008 kgCO2,eq kgbCOD-1), due to the chemical interaction between hydroxylamine and the disinfectant agent (hypochlorite). The specific emission factor of the biological aerated tank was 0.00112 kgCO2,eq kgbCOD-1. The average direct CO2 emission was equal to 0.068 kgCO2 kgbCOD-1 from the activated sludge tank and to 0.00017 kgCO2 kgbCOD-1 from the secondary clarifier. Therefore, taking into account the contribution of both direct N2O and CO2 emissions, values of 0.069 kgCO2,eq kgbCOD-1, 0.008 kgCO2,eq kgbCOD-1 and 0.00022 kgCO2,eq kgbCOD-1, were found for the net CFP of the aerated compartment, the disinfection unit and the clarifier, respectively. The plant energy Footprint (eFP) was also evaluated, confirming that the aeration system is the major contributor to energy consumption, as well as to indirect CO2 emission, with a specific eFP of 1.49 kWh kgbCOD-1.

Effects of body mass on microstructural features of the osteochondral unit: A comparative analysis of 37 mammalian species.

Since Galileo's days the effect of size on the anatomical characteristics of the structural elements of the body has been a subject of interest. However, the effects of scaling at tissue level have received little interest and virtually no data exist on the subject with respect to the osteochondral unit in the joint, despite this being one of the most lesion-prone and clinically relevant parts of the musculoskeletal system. Imaging techniques, including Fourier transform infrared imaging, polarized light microscopy and micro computed tomography, were combined to study the response to increasing body mass of the osteochondral unit. We analyzed the effect of scaling on structural characteristics of articular cartilage, subchondral plate and the supporting trabecular bone, across a wide range of mammals at microscopic level. We demonstrated that, while total cartilage thickness scales to body mass in a negative allometric fashion, thickness of different cartilage layers did not. Cartilage tissue layers were found to adapt to increasing loads principally in the deep zone with the superficial layers becoming relatively thinner. Subchondral plate thickness was found to have no correlation to body mass, nor did bone volume fraction. The underlying trabecular bone was found to have thicker trabeculae (r=0.75, p<0.001), as expected since this structure carries most loads and plays a role in force mitigation. The results of this study suggest that the osteochondral tissue structure has remained remarkably preserved across mammalian species during evolution, and that in particular, the trabecular bone carries the adaptation to the increasing body mass.

The ISTH Bleeding Assessment Tool and the risk of future bleeding.

Essentials ISTH Bleeding Assessment Tool (ISTH-BAT) is used to assist the diagnosis of bleeding disorders. We examined whether the ISTH-BAT is capable of predicting the risk of future bleeding. 136 subjects were administered the ISTH-BAT and followed for up to four years. The ISTH-BAT score failed to predict the risk of future bleeding. SUMMARY: Background The ISTH Bleeding Assessment Tool (ISTH-BAT) is a diagnostic tool used in subjects with suspected inherited bleeding disorders. Aim To evaluate whether the ISTH-BAT, applied at first work-up in a tertiary-care center, predicts the risk of subsequent bleeding events. Methods This was an observational cohort study including all consecutive subjects, of either sex and any age, referred between 2011 and 2015 because of a suspected bleeding disorder. The analysis was restricted to those with an ISTH-BAT score of ≥ 3. Incidence rates (IRs) of major bleeding (MB) and clinically relevant non-major bleeding (CRNMB) events were calculated as the number of events over accrued person-years. The main analysis was performed with Cox regression analysis, assessing an ISTH-BAT score of ≤ 5 versus a score of > 5, as well as the score as a continuous variable, and various covariates (sex, age, and presence/absence of a final diagnosis). Results One hundred and thirty-six subjects had a median ISTH-BAT score of 4 (range 3-18). Eleven subjects (8.1%) had a bleeding event during follow-up (one MB event; 10 CRNMB events). The overall IR of bleeding events per 100 person-years was 3.7 (95% confidence interval [CI] 1.8-6.6). No difference was observed between subjects with an ISTH-BAT score of ≤ 5 and those with a score of > 5 (hazard ratio [HR] 1.2, 95% CI 0.3-4.6). The results were similar when the ISTH-BAT score was considered as a continuous variable (HR 1.1, 95% CI 0.9-1.4). The IR of bleeding was increased in individuals with a diagnosis of a hemostatic defect (IR of 7.5 per 100 person-years; HR 3.0, 95% CI 0.8-11.8). Conclusions The ISTH-BAT does not identify patients at increased risk of future bleeding events.

Immunochip analysis identifies novel susceptibility loci in the human leukocyte antigen region for acquired thrombotic thrombocytopenic purpura.

Essentials Genetic predisposition to acquired thrombotic thrombocytopenic purpura (aTTP) is mainly unknown. Genetic risk factors for aTTP were studied by Immunochip analysis and replication study. Human leukocyte antigen (HLA) variant rs6903608 conferred a 2.5-fold higher risk of developing aTTP. rs6903608 and HLA-DQB1*05:03 may explain most of the HLA association signal in aTTP. Click to hear Dr Cataland's presentation on acquired thrombotic thrombocytopenic purpura SUMMARY: Background Acquired thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening thrombotic microangiopathy associated with the development of autoantibodies against the von Willebrand factor-cleaving protease ADAMTS-13. Similarly to what has been found for other autoimmune disorders, there is evidence of a genetic contribution, including the association of the human leukocyte antigen (HLA) class II complex with disease risk. Objective To identify novel genetic risk factors in acquired TTP. Patients/Methods We undertook a case-control genetic association study in 190 European-origin TTP patients and 1255 Italian healthy controls by using the Illumina Immunochip. Replication analysis in 88 Italian cases and 456 controls was performed with single-nucleotide polymorphism (SNP) TaqMan assays. Results and conclusion We identified one common variant (rs6903608) located within the HLA class II locus that was independently associated with acquired TTP at genome-wide significance and conferred a 2.6-fold increased risk of developing a TTP episode (95% confidence interval [CI] 2.02-3.27, P = 1.64 × 10-14 ). We also found five non-HLA variants mapping to chromosomes 2, 6, 8 and X that were suggestively associated with the disease: rs9490550, rs115265285, rs5927472, rs7823314, and rs1334768 (nominal P-values ranging from 1.59 × 10-5 to 7.60 × 10-5 ). Replication analysis confirmed the association of HLA variant rs6903608 with acquired TTP (pooled P = 3.95 × 10-19 ). Imputation of classic HLA genes followed by stepwise conditional analysis revealed that the combination of rs6903608 and HLA-DQB1*05:03 may explain most of the HLA association signal in acquired TTP. Our results refined the association of the HLA class II locus with acquired TTP, confirming its importance in the etiology of this autoimmune disease.

Occurrence, causes, and outcome of delirium in patients with advanced cancer: a prospective study.

CONTEXT: Delirium impedes communication and contributes to symptom distress in patients with advanced cancer. There are few prospective data on the reversal of delirium in this population. OBJECTIVES: To evaluate the occurrence, precipitating factors, and reversibility of delirium in patients with advanced cancer. DESIGN: Prospective serial assessment in a consecutive cohort of 113 patients with advanced cancer. Precipitating factors were examined using standardized criteria; 104 patients met eligibility criteria. SETTING: Acute palliative care unit in a university-affiliated teaching hospital. MAIN OUTCOME MEASURES: Delirium occurrence and reversal rates, duration, and patient survival. Strengths of association of various precipitating factors with reversal were expressed as hazard ratios (HRs) in univariate and multivariate analyses. RESULTS: On admission, delirium was diagnosed in 44 patients (42%), and of the remaining 60, delirium developed in 27 (45%). Reversal of delirium occurred in 46 (49%) of 94 episodes in 71 patients. Terminal delirium occurred in 46 (88%) of the 52 deaths. In univariate analysis, psychoactive medications, predominantly opioids (HR, 8.85; 95% confidence interval [CI], 2.13-36.74), and dehydration (HR, 2.35; 95% CI, 1.20-4.62) were associated with reversibility. Hypoxic encephalopathy (HR, 0.39; 95% CI, 0.19-0.80) and metabolic factors (HR, 0.44; 95% CI, 0.21-0.91) were associated with nonreversibility. In mulitivariate analysis, psychoactive medications (HR, 6.65; 95% CI, 1.49-29.62), hypoxic encephalopathy (HR, 0.32; 95% CI, 0.15-0.70), and nonrespiratory infection (HR, 0.23; 95% CI, 0.08-0.64) had independent associations. Patients with delirium had poorer survival rates than controls (P<.001). CONCLUSIONS: Delirium is a frequent, multifactorial complication in advanced cancer. Despite its terminal presentation in most patients, delirium is reversible in approximately 50% of episodes. Delirium precipitated by opioids and other psychoactive medications and dehydration is frequently reversible with change of opioid or dose reduction, discontinuation of unnecessary psychoactive medication, or hydration, respectively.

Test-positive rate at CT colonography is increased by rectal bleeding and/or unexplained weight loss, unlike other common gastrointestinal symptoms.

PURPOSE: We evaluated the rate of significant colonic and extra-colonic abnormalities at computed tomography colonography (CTC), according to symptoms and age. MATERIALS AND METHODS: We retrospectively evaluated 7361 consecutive average-risk subjects (3073 males, average age: 60.3 ± 13.9; range 18-96 years) for colorectal cancer (CRC) who underwent CTC. They were divided into three groups according to clinical symptoms: 1343 asymptomatic individuals (group A), 899 patients with at least one "alarm" symptom for CRC, including rectal bleeding and unexplained weight loss (group C), and 5119 subjects with other gastrointestinal symptoms (group B). Diagnostic and test-positive rates of CTC were established using optical colonoscopy (OC) and/or surgery as reference standard. In addition, clinically significant extra-colonic findings were noted. RESULTS: 903 out of 7361 (12%, 95% confidence interval (CI) 0.11-0.13) subjects had at least one clinically significant colonic finding at CTC. CTC true positive fraction and false positive fraction were respectively 637/642 (99.2%, 95%CI 0.98-0.99) and 55/692 (7.95%, 95%CI 0.05-0.09). The pooled test-positive rate in group C (138/689, 20.0%, 95%CI 0.17-0.23) was significantly higher than in both groups A (79/1343, 5.9%, 95%CI 0.04-0.07) and B (420/5329, 7.5%, 95%CI 0.07-0.08) (p < 0.001). Aging and male gender were associated to a higher test positive rate. The rate of clinically significant extra-colonic findings was significantly higher in group C (44/689, 6.4%, 95%CI 0.04-0.08) versus groups A (26/1343, 1.9%, 95%CI 0.01-0.02) and B (64/5329, 1.2%, 95%CI 0.01-0.02) (p < 0.001). CONCLUSION: Both test-positive and significant extra-colonic finding rates at CTC are significantly increased in the presence of "alarm" gastrointestinal symptoms especially in older patients.

The impact of delirium on the circadian distribution of breakthrough analgesia in advanced cancer patients.

Most cancer patients will experience pain requiring opioid therapy during their illness. Standard opioid therapy includes fixed scheduled doses and so-called "rescue" doses for breakthrough pain. Circadian rhythms seem to influence the expression of pain and the responsiveness to analgesic medication. Delirium is a common complication in advanced cancer patients and it also may modify the expression of pain and the use of analgesic medication. We reviewed the circadian distribution of breakthrough analgesia (BTA) doses in 104 advanced cancer patients who were part of a prospective study of the occurrence of delirium. We found that the circadian distribution of BTA is significantly different from a random distribution in the case of patients with and without delirium. Patients without delirium tended to use more BTA (P < 0.001) in the morning, whereas patients with delirium tended to use more BTA in the evening and at night (P = 0.02). We conclude that delirium is associated with changes in the circadian distribution of BTA, which is possibly related to reversal of the normal circadian rhythm.

Opioid type and other clinical predictors of laxative dose in advanced cancer patients: a retrospective study.

BACKGROUND: Constipation is a frequent and underdiagnosed complication in patients with advanced cancer. Constipation in this population is multifactorial, but the use of opioids is one of the main causes. The purpose of this retrospective study was to establish the association between opioid type and laxative dose, as well as the contribution of other clinical factors in advanced cancer patients admitted to a palliative care unit. METHODS: The records of consecutive patients admitted to the Acute Palliative Care Unit at the Grey Nuns Hospital between December 1995 and January 1997 were reviewed. Criteria of eligibility were the presence of cancer pain treated by opioids (oral and subcutaneous morphine and hydromorphone, oral methadone), oral laxative treatment capable of achieving at least one bowel movement every 3 days, and the absence of bowel obstruction or colostomy. During period(s) of stable analgesic doses, the charts were reviewed for demographic and clinical characteristics, average number of bowel movements, daily laxative doses, doses and type of opioid, laxative/opioid dose ratio (LOR) (calculated by dividing the total laxative dose by the total opioid dose), functional and cognitive status, food intake, and level of calcium, albumin, and potassium. RESULTS: Forty-nine evaluable patients were identified. The LOR in patients receiving oral opioids was 0.15 +/- 0.19 vs. 0.18 +/- 0.17 in patients on parenteral opioids (p > 0.2). The LOR in patients receiving methadone was 0.025 +/- 0.027 as compared to 0.24 +/- 0.23 in patients receiving morphine and 0.17 +/- 0.13 in patients on hydromorphone (p < 0.0001). We found a strong association between LOR and abdominal involvement (p < 0.0006), opioid type (p < 0.0001), age (p < 0.0001), and female gender (p < 0.034). There were no significant correlation between LOR and functional status, cognitive status, food intake, and level of calcium or potassium. CONCLUSION: We conclude that laxative dose needs to be titrated on an individualized basis. The LOR is lower in patients receiving methadone and in those of male gender, younger age, and absence of abdominal involvement.

Sedation for delirium and other symptoms in terminally ill patients in Edmonton.

The use of sedation and the management of delirium and other difficult symptoms in terminally ill patients in Edmonton has been reported previously. The focus of this study was to assess the prevalence in the Edmonton region of difficult symptoms requiring sedation at the end of life. Data were collected for 50 consecutive patients at each of (a) the tertiary palliative care unit, (b) the consulting palliative care program at the Royal Alexandra Hospital (acute care), and (c) three hospice inpatient units in the city. Patients on the tertiary palliative care unit were significantly younger. Assessments confirmed the more problematic physical and psychosocial issues of patients in the tertiary palliative care unit. These patients had more difficult pain syndromes and required significantly higher doses of daily opioids. Approximately 80% of patients in all three settings developed delirium prior to death. Pharmacological management of this problem was needed by 40% in the acute care setting, and by 80% in the tertiary palliative care unit. The patients sedated varied from 4% in the hospice setting to 10% in the tertiary palliative care unit. Of the 150 patients, nine were sedated for delirium, one for dyspnea. The prevalence of delirium and other symptoms requiring sedation in our area is relatively low compared to others reported in the literature. Demographic variability between the three Edmonton settings highlights the need for caution in comparing results of different palliative care groups. It is possible that some variability in the use of sedation internationally is due to cultural differences. The infrequent deliberate use of sedation in Edmonton suggests that improved management has resulted in fewer distressing symptoms at the end of life. This is of benefit to patients and to family members who are with them during this time.

Ultrastructure of CD57+ cells isolated from human tonsils or blood.

The presence of CD4+, CD57+ T cells in the germinal centers has been reported by several authors. The CD57 antigen is also expressed by natural killer (NK) cells. We purified CD57+ cells from human tonsils and blood by microdissection, rosetting with sheep red blood cells and magnetic cell sorting (MACS) and examined the ultrastructural morphology of these cells. Clear differences were found in cell aspect: blood NK contained large granules which were not found in the tonsillar CD57+ cells. These latter appeared medium-sized and not fully activated. After immunolabeling, the tonsillar CD57+ cells were mainly found in the light zone of the germinal centers.

[Lupic nephropathy in childhood: morphologic analysis of 18 cases]. / Níveis séricos de IgE total em crianças brasileiras normais no primeiro ano de vida.

Serum IgE concentration was determined in 17 newborn and 171 children with ages between 1 and 12 months. In the first group, blood was taken from the umbilical cord, and in the second, we used a periferic blood sample. The selection implied the exclusion of children with any suspicion of atopic disease, family history of atopy and recent viral infection. The serum IgE concentration was determined by enzyme linked immunoabsorbent assay (PRIST). The sex, race ( white and non white) and age were analyzed in the children studied. During a follow-up period (24 months) seven children (3,7%) developed atopic symptoms. The serum IgE concentration of the groups studied was higher than in other studies. The mean IgE in each group was as follows : newborns = 0.24 IU/ml; 1-3 months = 1.57 IU/ml; 4-6 months = 7.72 IU/ml; 7-9 months 12.07 IU/ml; 10-12 months = 12.14 IU/ml.

[Treatment of cancer pain: the role of co-analgesics]. / Traitement de la douleur cancereuse: le rôle des coanalgésiques.

Opioid analgesics are widely acknowledged as the most important drugs for the treatment of chronic cancer pain. Although these drugs can in most cases control severe pain, even when they are used appropriately, they may produce new symptoms or exacerbate preexisting symptoms, most notably nausea and somnolence. The combination of severe pain, anorexia, chronic nausea, asthenia, and somnolence is a frequent finding in patient with advanced cancer. An adjuvant drug should meet at least one of the following criteria: 1) to increase the analgesic effect of opioids; 2) to decrease their toxicity; 3) to improve others symptoms associated with terminal cancer. Many drugs, such as nonsteroidal antiinflammatory agents, tricyclic antidepressants, corticosteroids, benzodiazepines, amphetamines, antiemetics, oral local anesthetics and bisphosphonates have been suggested to have adjuvant analgesic effects. Unfortunately, most of the evidence for the effects of these drugs is anedoctal. Controlled clinical trials are badly needed to precise the indications and the risk/benefit ratios of these agents, some of which have significant toxicity and could potentially aggravate narcotics toxicity.