In vivo induction of the nitric oxide pathway in hepatocytes after injection with irradiated malaria sporozoites,malaria blood parasites or adjuvants

The mechanisms responsible for malarial immunity induced by repetitive injections of X-irradiated sporozoites have not been fully established. We demonstrate here that a single injection of irradiated sporozoites induced, as soon as 24 h after, a non-permissive state to hepatocyte reinfection with sporozoites in vitro. The same effect was observed when malarial blood forms, irradiated promastigotes of Leishmania infantum, adjuvants (muramyl dipeptide, poly acidylic uridylic) or interferon-γ was injected. Activation of the nitric oxide (NO) pathway in the hepatocyte by these factors was found to be responsible for hepatocyte refractory status. Additionally, this metabolic pathway is involved in protection given by repeated injections of irradiated sporozoites since protection could be reversed by treating mice at the time of sporozoite challenge with a competitive inhibitor (N^G-monomethyl-L-arginine) of the NO pathway. These results suggest that, in view of an antisporozoite vaccine, further studies are needed to find out how to activate specifically a long-lasting nonspecific immune response.     

Written patient information: a review of the literature*

In the United States during the 1940s Flesch and Gunning pioneered the movement to improve the comprehensibility of government documents Since that time the provision of comprehensible information to the general public has become increasingly important Indeed, most computer programs have the facility to assess what percentage of the population will understand certain forms of written information Vast quantities of written patient information have been produced over the decades and more are being produced daily This literature review sets out to provide an insight into the studies which have looked at the value and purpose of such literature Considering the amount of written patient information in existence the amount of research into this interesting subject is small Many concepts have to be considered Is this information of any use to patients? Can they understand and recall it and does it increase compliance? Are patients satisfied with the amount, quality and detail of written information? If health professionals are to inform their patients fully, written information is an area which should be more fully researched for ethical, quality and economic reasons     

Family Factors Associated with Aggressive Symptomatology in Boys with Attention Deficit Hyper activity Disorder: A Research Note

This study tested whether parent and child affective attitudes and interactional behavior co-varied with the presence or absence of associated aggressive symptomatology in families with an attention deficit hyperactivity disorder (ADHD) child. Affective attitudes of both parents and their ADHD sons were studied using a modified measure of expressed emotion, the five minute speech sample (FMSS-EE), in 29 families. A direct interaction task was also used to measure verbal and non-verbal communication. FMSS-EE status predicted parental interactional behavior, but the degree of child aggressiveness did not. The child's behavior towards parents, however, was highly correlated with their aggressiveness but not their EE status regarding their parents, despite the fact that child and parent EE were highly correlated. The study supports the notion that aggressiveness and a negative family climate may be independent factors in determining the long-term course of ADHD children.     

Accuracy and quality of immunization information systems in forty-one low income countries

Objectives  To measure the accuracy and quality of immunization information systems in a range of low-income countries eligible to receive GAVI support.
Methods  The Data Quality Audit (DQA) uses a WHO validated, standard methodology to compare data collected from health unit (HU) records of immunizations administered with reports of immunizations at central level and to collect quality indicators of the reporting system. The verification factor (VF), as a measure of accuracy, expresses the proportion of immunizations reported at national level that can be tracked down to the HU. A VF of 80% or above entitles countries to receive additional GAVI financial support. Quality indicators are assigned points which were summed to obtain quality scores (QS) at national, district and HU levels. DQAs included here were conducted between 2002 and 2005 in 41 countries, encompassing 1082 primary healthcare units in 188 randomly selected districts.
Results  Almost half of countries obtained a VF below 80% and only nine showed consistently high VF and QS scores. The most frequent weaknesses in the information systems were inconsistency of denominators used to estimate coverage, poor availability of guidelines (e.g. for late reporting), incorrect estimations of vaccine wastage and lack of feedback on immunization performance. In all six countries that failed a first DQA and undertook a second DQA, the VF and all QSs improved, not all of them statistically significantly.
Conclusions  The DQA is a diagnostic tool to reveal a number of crucial problems that affect the quality of immunization data in all tiers of the health system. It identifies good performance at HU and district levels which can be used as examples of best practices. The DQA methodology brings data quality issues to the top of the agenda to improve the monitoring of immunization coverage.     

Reciprocal interactions between β1-integrin and epidermal growth factor receptor in three-dimensional basement membrane breast cultures: A different perspective in epithelial biology

Anchorage and growth factor independence are cardinal features of the transformed phenotype. Although it is logical that the two pathways must be coregulated in normal tissues to maintain homeostasis, this has not been demonstrated directly. We showed previously that down-modulation of β1-integrin signaling reverted the malignant behavior of a human breast tumor cell line (T4–2) derived from phenotypically normal cells (HMT-3522) and led to growth arrest in a three-dimensional (3D) basement membrane assay in which the cells formed tissue-like acini (14). Here, we show that there is a bidirectional cross-modulation of β1-integrin and epidermal growth factor receptor (EGFR) signaling via the mitogen-activated protein kinase (MAPK) pathway. The reciprocal modulation does not occur in monolayer (2D) cultures. Antibody-mediated inhibition of either of these receptors in the tumor cells, or inhibition of MAPK kinase, induced a concomitant down-regulation of both receptors, followed by growth-arrest and restoration of normal breast tissue morphogenesis. Cross-modulation and tissue morphogenesis were associated with attenuation of EGF-induced transient MAPK activation. To specifically test EGFR and β1-integrin interdependency, EGFR was overexpressed in nonmalignant cells, leading to disruption of morphogenesis and a compensatory up-regulation of β1-integrin expression, again only in 3D. Our results indicate that when breast cells are spatially organized as a result of contact with basement membrane, the signaling pathways become coupled and bidirectional. They further explain why breast cells fail to differentiate in monolayer cultures in which these events are mostly uncoupled. Moreover, in a subset of tumor cells in which these pathways are misregulated but functional, the cells could be “normalized” by manipulating either pathway.     

Benign paroxysmal positional nystagmus in hospitalized subjects receiving ototoxic medications.

OBJECTIVE: To investigate the occurrence of benign paroxysmal positional nystagmus in subjects undergoing treatment with potentially ototoxic medications. STUDY DESIGN: Prospective and retrospective record reviews. SETTING: Tertiary referral neurotology clinic; clinical research and technology center. SUBJECTS: Ninety-nine hospitalized subjects undergoing treatment of infectious disease or carcinoma with potentially ototoxic medications. INTERVENTIONS: Records review, tests of vestibular function. MAIN OUTCOME MEASURE: Results of Hallpike positional tests for benign paroxysmal positional nystagmus (electro-oculography). RESULTS: Forty-one (41%) of 99 subjects were female and 58 (59%) were male. Age range was 15 to 73 years (mean, 47 years). Forty-nine (50%) of 99 subjects had an unequivocally positive Hallpike test for benign paroxysmal positional nystagmus in one or both ears. The occurrence of benign paroxysmal positional nystagmus in the Hallpike-positive population was distributed equally across age decades. Of the 49 subjects with benign paroxysmal positional nystagmus, 22 (44%) were female and 27 (56%) were male. CONCLUSIONS: Benign paroxysmal positional nystagmus is the most common cause of vertigo in the general population, including subjects receiving ototoxic drugs. Complaints of vertigo in subjects receiving ototoxic drugs therefore may or may not indicate onset of ototoxicity. Occurrence of benign paroxysmal positional nystagmus in subjects receiving ototoxic drugs was independent of gender or age. The high occurrence rate of benign paroxysmal positional nystagmus in subjects receiving potentially ototoxic medications is consistent with the observation that benign paroxysmal positional nystagmus occurs in combination with many pathologic conditions. Benign paroxysmal positional nystagmus presenting in subjects receiving ototoxic drugs may complicate the clinical identification of ototoxicity and obfuscate clinical decision-making processes.