Introduction to Tissular and Cellular Engineering

Most human tissues do not regenerate spontaneously, which is why cellular therapies and tissular engineering are promising alternatives. The principle is simple: cells are sampled in a patient and introduced in the damaged tissue or in a tridimentional porous support and cultivated in a bioreactor in which the physico-chemical and mechanical parameters are controlled. Once the tissues (or the cells) are mature they may be implanted. In parallel, the development of biotherapies with stem cells …     

Which medical error to disclose to patients and by whom? Public preference and perceptions of norm and current practice

Background

HIV prevention trials conducted among disadvantaged vulnerable at-risk populations in developing countries present unique ethical dilemmas. A key concern in bioethics is the validity of informed consent for trial participation obtained from research subjects in such settings. The purpose of this study was to investigate the effectiveness of a continuous informed consent process adopted during the MDP301 phase III vaginal microbicide trial in Mwanza, Tanzania.

Methods

A total of 1146 women at increased risk of HIV acquisition working as alcohol and food vendors or in bars, restaurants, hotels and guesthouses have been recruited into the MDP301 phase III efficacy and safety trial in Mwanza. During preparations for the trial, participatory community research methods were used to develop a locally-appropriate pictorial flipchart in order to convey key messages about the trial to potential participants. Pre-recorded audio tapes were also developed to facilitate understanding and compliance with gel-use instructions. A comprehension checklist is administered by clinical staff to all participants at screening, enrolment, 12, 24, 40 and 50 week follow-up visits during the trial. To investigate women's perceptions and experiences of the trial, including how well participants internalize and retain key messages provided through a continuous informed consent process, a random sub-sample of 102 women were invited to participate in in-depth interviews (IDIs) conducted immediately after their 4, 24 and 52 week follow-up visits.

Results

99 women completed interviews at 4-weeks, 83 at 24-weeks, and 74 at 52 weeks (a total of 256 interviews). In all interviews there was evidence of good comprehension and retention of key trial messages including that the gel is not currently know to be effective against HIV; that this is the key reason for conducting the trial; and that women should stop using gel in the event of pregnancy.

Conclusions

Providing information to trial participants in a focussed, locally-appropriate manner, using methods developed in consultation with the community, and within a continuous informed-consent framework resulted in high levels of comprehension and message retention in this setting. This approach may represent a model for researchers conducting HIV prevention trials among other vulnerable populations in resource-poor settings.

Trial registration

Current Controlled Trials ISRCTN64716212     

Three-Month-Olds’ Brain Responses to Upright and Inverted Faces and Cars

We examined the processing of upright and inverted faces and cars in 3-month-old infants applying an event-related-potentials paradigm. The current study is the first to contrast human faces with an object category, cars, in a within-subjects design with infants. N290 amplitude was larger for inverted than upright faces, whereas no inversion effect was observed for cars. Moreover, N290 latency was enhanced for inverted faces and cars. This indicates that neural processing may already be partly face-specific in young infants.     

Face temperature and cardiorespiratory responses to wind in thermoneutral and cool subjects exposed to −10 °C

The effects of the thermal state of the body (slightly cool and neutral) and moderate wind speeds on face temperature, blood pressure, respiratory function and pain sensation during cold exposure were studied on eight healthy male subjects. They were dressed in cold-protective clothing and preconditioned at +20 °C (TN) and −5 °C (CO) for 60 min, then exposed to −10 °C and 0 m · s⁻¹ (NoW), 1 (W1) and 5 (W5) m · s⁻¹ wind for 30 min. Thus, each individual was exposed six times. The exposure to wind entailed a combination of strong cooling of the bare face and mild body cooling. The forehead, cheek and nose temperatures decreased during cold exposure, and the decrease was greater at higher air velocities (P < 0.0001). All subjects reported pain sensations at 5 m · s⁻¹. At the end of exposure only the nose temperature was significantly lower in CO than in TN subjects; it was about 2 °C and reached 0 °C in two experiments. The systolic and diastolic blood pressure (SBP and DBP, respectively) increased significantly by 7.7 and 5.9 mmHg, respectively, during preconditioning at −5 °C, but did not change at +20 °C. SBP and DBP increased during exposure to −10 °C in TN by approximately 9 mmHg. However, the total average increase of blood pressure (1–90 min) was similar in TN and CO (SBP 15 mmHg and DBP 13 mmHg). SBP and DBP increased more during exposure to 5 m · s⁻¹ at −10 °C than NoW. Blood pressure responses as observed in this study (SBP and DBP up to 51 and 45 mmHg, respectively) are potential health risks for hypertensive individuals and angina patients. Respiratory functions (FVC, FEV₁) were reduced by about 3% by the cold (−5 and −10 °C) compared to pre-experiment values. Furthermore, the Wind Chill Index seems to underestimate the cooling power of 5 m · s⁻¹ at −10 °C of bare skin (e.g. face). Therefore it needs to be revised and we suggest that it is expanded to include risk levels for pain sensation. Accepted: 29 May 2000     

Stability and immunoreactivity of glycinin and β-conglycinin to hydrolysis in vitro

The present study was to compare the stability and immunoreactivity of glycinin and β-conglycinin to hydrolysis with pepsin, trypsin or cooperation of the two enzymes for different time intervals (0.5, 1, 15, 30, 60 and 120 min) at different ratios of enzyme/substrate (1:100, 1:10, 1:1 and 10:1) in vitro. The results showed that the immunoreactivity was positively related with stability of glycinin (r=0.776, P<0.05) and β-conglycinin (r=0.851, P<0.05). B polypeptide chain of glycinin was resistant to hydrolysis with trypsin, and β subunit of β-conlycinin was not liable to hydrolysis with pepsin. The two above proteins were little or not affected by incubation time and the enzyme/substrate ratio, while others' hydrolysed degree got higher with prolonging incubation time, and the hydrolysis accelerated with increasing enzyme/substrate ratio. Our results indicated digestive enzyme, incubation time and enzyme/substrate ratio had effects on stability and immunoreactivity of allergenic proteins. The most effective hydrolysis was cooperation of the two enzymes for glycinin and trypsin for β-conglycinin.     

Women and HIV: when to test?

The devastating effects of HIV infection in women can be altered dramatically with new therapies. Certain clinical syndromes, including oral thrush, diffuse lymphadenopathy, wasting, unexplained fevers, or oral hairy leukoplakia, clearly indicate a need for HIV testing. This article reviews other clinical syndromes, both gender-specific and non-gender-specific, that may prompt the practitioner to consider HIV testing.     

Hypersensitivity reactions and anaphylaxis to checkpoint inhibitor–monoclonal antibodies and desensitization

ObjectiveTo review type 1 hypersensitivity reactions and anaphylaxis to checkpoint inhibitor–monoclonal antibodies and its management with drug desensitization.Data SourcesEnglish-language literature on MEDLINE regarding hypersensitivity, anaphylaxis, and checkpoint inhibitor–monoclonal antibodies.Study SelectionsReferences were selected based on relevance, novelty, robustness, and applicability.ResultsThere are well-known tissue toxicities associated to checkpoint inhibitors, but hypersensitivity reactions and anaphylaxis have been underreported. The presentation of these reactions is based on clinical phenotypes with underlying endotypes identified by specific biomarkers. Drug desensitizations have been successfully applied to checkpoint inhibitor drugs to allow patients with cancer to receive first-line therapies. This review provides current best practices for the recognition and diagnosis of hypersensitivity reactions and anaphylaxis to checkpoint inhibitors and their management using drug desensitization.ConclusionHypersensitivity reactions and anaphylaxis have been identified as potential adverse effects induced by checkpoint inhibitor–monoclonal antibodies. Drug desensitization is a safe and effective treatment option for patients who experience hypersensitivity reactions in need of these monoclonal antibodies to improve cancer outcomes.     

Dendritic cells adhere to and transmigrate across lymphatic endothelium in response to IFN-α

Migration of DC into lymphatic vessels ferries antigenic cargo and pro-inflammatory stimuli into the draining LN. Given that tissues under the influence of viral infections produce type I IFN, it is conceivable that these cytokines enhance DC migration in order to facilitate an antiviral immune response. Cultured lymphatic endothelium monolayers pretreated with TNF-α were used to model this phenomenon under inflammatory conditions. DC differentiated in the presence of either IFN-α2b or IFN-α5 showed enhanced adhesion to cultured lymphatic endothelial cells. These pro-adhesive effects were mediated by DC, not the lymphatic endothelium, and correlated with increased DC transmigration across lymphatic endothelial cell monolayers. Transmigration was guided by chemokines acting on DC, and blocking experiments with mAb indicated a role for LFA-1. Furthermore, incubation of DC with IFN-α led to the appearance of active conformation epitopes on the CD11a integrin chains expressed by DC. Differentiation of mouse DC in the presence of IFN-α also increased DC migration from inflammed footpads toward popliteal LN. Collectively, these results indicate a role for type I IFN in directing DC toward LN under inflammatory conditions.     

Why does EBD need to diagnose and to therapy for patients,now?

G. Guyatt reported the first paper on Evidence Based Medicine(EBM) at 1991. Everybody could understand rapidly the necessary of EBM to diagnose and medical treat the patients from then. So, I will tell you the recent actions of EBLM committee of Japan Society of Clinical Laboratory Medicine (JSLM/C-EBLM) related with EBM. I define EBLM(Evidence-Based Laboratory Medicine) has the total functions to use the clinical laboratory data by evidence for the diagnosis and the therapy of patients. JSLM/C-EBLM was seted up at 1999 and supported EBD(Evidence-Based Diagnosis) Forums as the main action. JSLM/C-EBLM will make and use practically the new meta-analysis tools and educate about EBLM from now.     

Antimicrobial Agents Induce Monocytes to Release IL-1α, IL-6, and Tnf and Induce Lymphocytes to Release IL-4 and TNFτ

Abstract

Evaluation was carried out on the action of different antibiotics on the release of cytokines. Experiments were done in vitro on monocytes and on human lymphocytes. Results show that the majority of the antibiotics tested are able to induce the release of one or more cytokines from their respective producing cells. Among the β-lactams the most active were the cephalosporins (cephalexin, cefamandol, ceftazidin, and a sulbactam-ampxcillin combination) in inducing the release of TNF, IL-1α and IL-6 from monocytes, and releasing IL-4 and IFN-τ from lymphocytes. The sulbactam-ampicillin combination and cefamandole were extremely active in the production of IFN-τ. Among the lincosamides, clindamycine notably stimulated the release of TNF and IL-6, while lincomycine induced a notable increment of IL-4 from monocytes. Teicoplanin is a very strong inducer of TNF, IL-1α and IL-6.     

Radiosensitivity of human ovarian carcinoma and melanoma cells to γ-rays and protons

Introduction

Proton radiation offers physical advantages over conventional radiation. Radiosensitivity of human 59M ovarian cancer and HTB140 melanoma cells was investigated after exposure to γ-rays and protons.

Material and methods

Irradiations were performed in the middle of a 62 MeV therapeutic proton spread out Bragg peak with doses ranging from 2 to 16 Gy. The mean energy of protons was 34.88 ±2.15 MeV, corresponding to the linear energy transfer of 4.7 ±0.2 keV/µm. Irradiations with γ-rays were performed using the same doses. Viability, proliferation and survival were assessed 7 days after both types of irradiation while analyses of cell cycle and apoptosis were performed 48 h after irradiation.

Results

Results showed that γ-rays and protons reduced the number of viable cells for both cell lines, with stronger inactivation achieved after irradiation with protons. Surviving fractions for 59M were 0.91 ±0.01 for γ-rays and 0.81 ±0.01 for protons, while those for HTB140 cells were 0.93 ±0.01 for γ-rays and 0.86 ±0.01 for protons. Relative biological effectiveness of protons, being 2.47 ±0.22 for 59M and 2.08 ±0.36 for HTB140, indicated that protons provoked better cell elimination than γ-rays. After proton irradiation proliferation capacity of the two cell lines was slightly higher as compared to γ-rays. Proliferation was higher for 59M than for HTB140 cells after both types of irradiation. Induction of apoptosis and G2 arrest detected after proton irradiation were more prominent in 59M cells.

Conclusions

The obtained results suggest that protons exert better antitumour effects on ovarian carcinoma and melanoma cells than γ-rays. The dissimilar response of these cells to radiation is related to their different features.     

How to Measure Scapholunate and Cobb’s Angles on MRI and CT

The measurement of angles between anatomical structures is common in radiological and orthopedic practice. Frequently used measurements include scapholunate angle for assessment of wrist instability and Cobb's angle used for assessment of scoliosis. Measurements of these angles are easily performed on plain X-ray radiographs. However, the situation is more complicated when these measurements are to be performed on cross-sectional (CT or MRI) examinations. On some of the diagnostic workstations, it is not possible to perform angle measurements between the structures if they are not identified on the same image and are located on different images of the same projection or plane. We present a simple solution to measure angles between structures on different images that can be used both in CT and MR.     

Sensitivity to ether anesthesia and to γ-rays in mutagen-sensitive strains of Drosophila melanogaster

An ether-resistant strain of Drosophila melanogaster, Eth-29, has previously been found to be radiosensitive. Some mutagen-sensitive strains are known to be hypersensitive to X-rays in larvae. The correlation between sensitivities to ether anesthesia and to y-rays was examined in adult flies of 12 mutagen-sensitive strains and 6 control strains. A wide variation in sensitivities to ether anesthesia, γ-ray knock-down and γ-ray lethality was demonstrated. No correlation between DNA-repair capacity and ether sensitivity or γ-ray knock-down sensitivity was shown. Only mei-9 and mus201, which are deficient in excision repair, as well as Eth-29 were found to be sensitive to γ-ray lethality. These findings indicate that the targets for ether anesthesia, knock-down and lethality may be different. Lethality appears to be caused by DNA damage, while the other 2 endpoints appear not to be related to DNA damage.