Natural latex allergy. Patient management: from clinic to prevention. A review

The widespread use of latex devices has been followed, in the last 25 years, by an increase in IgE mediated sensitization. The clinical manifestations of latex allergy affect the skin (urticaria and angioneurotic oedema), the lower and the upper respiratory tracts (rhinoconjunctivitis, asthma and glottis oedema), and the cardiovascular system (anaphylaxis). There is also an anaphylactic risk during surgery and invasive diagnostic procedures. Vegetable food cross-reacts with latex so that more than half of the patients show specific IgE against some food. Further than traditional groups at risk, as health care workers, other work categories have to be protected, because of the inappropriate use of latex gloves (food or drug industry workers, mechanics, panel beaters and so on). Recently the latex most important allergenic fractions have been characterized and recombinant allergens are now available. The recombinant allergens allow a better standardization of the extracts for diagnostic use, the production of safer extracts for immunotherapy as well as a more accurate evaluation of food cross-reactions. The recombinant allergens will allow a more accurate dosage of latex concentrations in air and in objects and, in future, to establish threshold limit values. The main aims of prevention are the replacement of latex with alternative elastomers, the reduction of work and extra work exposure and an efficient health survey in working environment. The use of latex gloves and devices among general population has to be discouraged. Specific immunotherapy has to be considered a second choice and restricted to highly qualified workers in order to realize a rehabilitation to their previous jobs. The actually obtained protection must be verified.     

Controlling the clonal spread of Pseudomonas aeruginosa infection.

To evaluate nosocomial infections due to imipenem-resistant and imipenem-susceptible Pseudomonas aeruginosa, a case-control study that included genotyping was performed. Hospitalization for more than 15 days was independently associated with infection with an imipenem-resistant organism. Sixty-seven percent of the imipenem-resistant isolates analyzed and 23% of the imipenem-susceptible isolates analyzed belonged to a single clone. Intervention led to a decrease in the number of infections due to imipenem-resistant and imipenem-susceptible P. aeruginosa.     

Staphylococcus aureus epidemic in a neonatal nursery: a strategy of infection control

The risk of nosocomial infection due to Staphylococcus aureus in fullterm newborns is higher under hospital conditions where there are overcrowded nurseries and inadequate infection control techniques. We report on an outbreak of skin infection in a Maternity Nursery (May 21, 2000) and the measures undertaken to bring the epidemic under control. These measures included: separating neonates already present in the nursery on August 23, 2000 from ones newly arriving by creating two different cohorts, one of neonates born before this date and one of neonates born later; restricting healthcare workers caring for S. aureus- infected infants from working with non-infected infants; disallowing carrier healthcare workers from caring for patients; introducing contact and droplet precautions (including the routine use of gowns, gloves, and mask); ensuring appropriate disinfection of potential sources of contamination. A representative number of isolates were typed by genomic DNA restriction length polymorphism analysis by means of pulsed-field gel electrophoresis (PFGE). Among the 227 cases of skin lesions, microbiological laboratory analyses confirmed that 175 were staphylococcal infections. The outbreak showed a gradual reduction in magnitude when the overcrowding of the Nursery was reduced by separating the newborns into the two different Nurseries (two cohorts). The genotyping of the strains by PFGE confirmed the nurse-to-newborn transmission of S. aureus. The measures adopted for controlling the S. aureus outbreak can, in retrospect, be assessed to have been very effective.     

Pharmacogenomics and analogues of the antitumour agent N6‐isopentenyladenosine

N⁶‐isopentenyladenosine (i⁶A), a member of the cytokinin family of plant hormones, has potent in vitro antitumour activity in different types of human epithelial cancer cell lines. Gene expression profile analysis of i⁶A‐treated cells revealed induction of genes (e.g., PPP1R15A, DNAJB9, DDIT3, and HBP1) involved in the negative regulation of cell cycle progression and reportedly up‐regulated during cell cycle arrest in stress conditions. Of 6 i⁶A analogues synthesized, only the 1 with a saturated double bond of the isopentenyl side chain had in vitro antitumour activity, although weaker than that of i⁶A, suggesting that i⁶A biological activity is highly linked to its structure. In vivo analysis of i⁶A and the active analogue revealed no significant inhibition of cancer cell growth in mice by either reagent. Thus, although i⁶A may inhibit cell proliferation by regulating the cell cycle, further studies are needed to identify active analogues potentially useful in vivo. © 2008 Wiley‐Liss, Inc.     

Molecular cytogenetic characterization of stem-like cancer cells isolated from established cell lines

There is indication that tumor growth is sustained by subpopulation of cells with stem-like features but little is known on their genomic characterization and their genetic stability. We report a detailed molecular cytogenetic characterization using Spectral Karyotyping and fluorescent in situ hybridization of parental serum-cultured adherent cells and their sphere-growing stem-like counterpart before and after differentiation from six cell lines established from solid tumors. Our findings indicate increased cytogenetic complexity in sphere-growing stem-like and their differentiated adherent cells compared to parental adherent component suggesting the existence within cell lines of heterogeneous and genetically unstable subpopulations of cells endowed with stem-like features.     

A study of tryptophan metabolism via serotonin in ventricular cerebrospinal fluid in HIV-1 infection using a neuroendoscopic technique

In this paper we report the study of tryptophan metabolism via serotonin in ventricular CSF in HIV-1 infection in order to investigate the origin of tryptophan metabolites in the human brain. The patients (n=4) were affected with non-communicating hydrocephalus. One of these also was suffering from HIV-1 infection. The CSF was withdrawn from different sites of the cerebral cavity with a neuroendoscopic procedure which allows an accurate exploration of all the cerebral ventricles. The measurement of tryptophan, 5-hydroxytryptophan, serotonin, 5-hydroxyindoleacetic acid, and melatonin was carried out by HPLC with fluorometric detection. In HIV-1 infection the highest concentration of tryptophan is present in the CSF of the choroid plexus; however, the levels are markedly lower than those in hydrocephalic individuals (control group). 5-Hydroxytryptophan CSF content is higher in HIV-1 infection than in hydrocephalic controls in all districts examined. Regarding serotonin, a great difference appears in the choroid plexus and in the pituitary recess between the HIV-1 infected patient and the control group. The values of 5-hydroxyindoleacetic acid are much lower in the CSF of the HIV-1 infected patient than in hydrocephalic controls. Melatonin levels appear to fluctuate largely but, in the HIV-1 infection, a great variability is present among the sites of CSF withdrawal. The third ventricle contains the highest concentration of melatonin and the choroid plexus and the pituitary recess the lowest. All the melatonin concentrations in HIV-1 infection are largely different than in hydrocephalic controls. This is the first report on the measurement of tryptophan metabolites via serotonin in ventricular CSF in HIV-1 infection.     

Role of functional performance in diagnosis of dementia in elderly people with low educational level living in Southern Italy

BACKGROUND AND AIMS: Diagnosis of dementia is often difficult in subjects with low educational level. Our aim was to evaluate the role of functional performance and the possibility of preferring scores of activities of daily living (ADL) and instrumental activities of daily living (IADL) in screening elderly people for diagnosis of dementia in a rural population of Southern Italy with a very high percentage of non-educated subjects. METHODS: a random sample of 300 residents, out of 1089 subjects over 60 years of age living in San Marcellino (Caserta, Campania), received door-to-door visit for information about their medical history, with clinical evaluation of general geriatric conditions, including the cumulative illness rating scale (CIRS). Dementia was diagnosed if subjects had a Clinical Dementia Rating score (CDR) > or = 1 and according to the criteria of DSMIV, but not according to scores on the Mini Mental State Examination (MMSE), ADL and IADL. Two hundred and nineteen normal subjects (NS) and 75 patients with dementia (DP) were evaluated. RESULTS: in NS, their mean age- and education-corrected MMSE score was 22.15 (lower than the normal cut-off value of 23.8) and 12.60 in DP (p<0.0001). In NS, the mean ADL score was higher than in DP (5.53 vs 2.64, p<0.0001); only age was correlated with ADL scores (coeff=-0.44, t=-4.557, p<0.0001). Assuming age as covariate, ADL scores highly differentiated DP from NS (F(1, 289)=26.083, p<0.0001). In both sexes, mean IADL scores were higher in NS than in DP (4.46 vs 1.80 in men, p<0.0001; 6.85 vs 2.31 in women, p<0.0001). Age and education did not influence IADL scores in men, but age greatly affected performance in women. IADL scores clearly differentiated NS from DP. In NS, a positive correlation was evident between ADL and IADL scores (r=0.234, p<0.0005), but neither scores correlated with the MMSE scores, even when correlation was performed separately for men and women. In DP, a strong correlation was observed between ADL and IADL scores (r=0.709, p<0.0001) and significant correlations were also evident between the scores of MMSE and both ADL (r=0.492,p<0.0001) and IADL (r=0.398, p<0.0004). CONCLUSIONS: in a rural community with a high prevalence of non-educated subjects, cognitive impairment is related to education, whereas independent functioning is limited mainly to age and not to cognition, if the latter remains (relatively) unimpaired. These results point to the importance of an "ecological" approach to the evaluation of elderly people, particularly those living in small rural communities, where education and the social environment may give rise to difficulties in diagnosis of dementia. The assessment of functional autonomy by ADL and IADL scales may be a better screening tool in diagnosing dementia than the MMSE scores.     

Effect of a novel vacuolar-H+-ATPase inhibitor on cell and tumor response to camptothecins

The vacuolar-H(+)-ATPase, functionally expressed in cell membranes, is known to play a relevant role in intracellular pH regulatory mechanisms, because it is implicated in pumping protons into the extracellular environment or in sequestrating excess protons into acidic vacuolar compartments. Because tumor cells exist in a hypoxic microenvironment and produce acidic metabolites, this regulatory mechanism is recognized as a protective function. This study was designed to investigate the effect of NiK-12192 [4-(5,6-dichloro-1H-indol-2-yl)-3-ethoxy-N-(2,2,6,6-tetramethyl-piperidin-4-yl)-benzamide], an indole derivative identified as an effective inhibitor of vacuolar-H(+)-ATPase, on the cytotoxic activity of two camptothecins, i.e., topotecan and SN-38 (7-ethyl-10-hydroxycamptothecin, the active metabolite of irinotecan). The cellular studies performed in two pairs of human colon carcinoma cell lines, i.e., LoVo and LoVo/DX (overexpressing P-glycoprotein) and HT29 and HT29/Mit (overexpressing breast cancer resistant protein), indicated an enhancement of the antiproliferative effect of camptothecins by concomitant exposure to subtoxic concentrations of NiK-12192. Studies of subcellular distribution indicated that whereas topotecan alone localized mainly in mitochondria and endoplasmic compartment, the simultaneous presence of NiK-12192 caused a cytoplasmic redistribution. In HT29/Mit cells, NiK-12192 reverted the pattern of acidification induced by topotecan. The potentiation of topotecan efficacy by NiK-12192 was documented by an increased efficacy of the combination in both the HT29 tumor xenografts, being more evident in the topotecan-resistant HT29/Mit tumor. In conclusion, the vacuolar-H(+)-ATPase inhibitor NiK-12192 was able to potentiate the cytotoxic/antitumor effects of camptothecins, either in in vitro or in in vivo systems. Such findings support a potential interest for the use of vacuolar-H(+)-ATPase inhibitors in combination therapy to improve camptothecin efficacy.