Assessing chemical exposures during military deployments

Before the first Persian Gulf War, military chemical concerns were focused on life-threatening/performance-impairing effects from exposures to chemical warfare agents. Now, hazards of concern include both high and low levels of chemical warfare agents and toxic industrial chemicals in air, soil, and water. The types of health effects considered have expanded to include both immediate, acute effects (mild and severe), and delayed or chronic outcomes. Because federal exposure standards are not applicable to deployed personnel, the U.S. Army Center for Health Promotion and Preventive Medicine established military-specific exposure guidelines in Technical Guide 230, Chemical Exposure Guidelines for Deployed Military Personnel. Methods used to develop the guidelines address toxicological data limitations, uniqueness of military populations and exposure scenarios, and a risk assessment process compatible with existing military operational risk management doctrine. The Technical Guide 230 helps ensure chemical hazards are addressed in various deployment scenarios.     

In vitro activity of extracts and constituents of Pelagonium against rapidly growing mycobacteria

Extracts of the roots of plants of the Geraniaceae family have been used for many years in South Africa as native herbal remedies and there is circumstantial evidence for efficacy in the treatment of pulmonary tuberculosis. We have examined dried roots of Pelargonium reniforme and P. sidoides for antibacterial activity against rapidly growing mycobacteria. Fractions with activity against Mycobacterium aurum and M. smegmatis were obtained from both plant species by bioassay-guided fractionation of n-hexane extracts and were found to contain mixtures of straight-chain fatty acids. Analysis by gas chromatography–mass spectrometry (GC–MS) of the corresponding fatty acid methyl esters revealed structures with chain lengths ranging from C12 to C26. Unsaturated compounds were analysed as the corresponding dimethyl disulfide adducts to determine double-bond positions. Active mixtures differed in the relative abundance of their components, but all contained 16:0 (palmitic), Δ⁹-18:1 (oleic) and Δ^9,12-18:2 (linoleic acid) as the major components. When tested against M. aurum, M. smegmatis and other rapidly growing mycobacteria (M. fortuitum, M. abscessus and M. phlei), all saturated compounds except 12:0 were devoid of antimycobacterial activity, whereas unsaturated compounds showed antimycobacterial activity related to their degree of unsaturation, their chain length and the bacterial species tested. The most potent compound was linoleic acid, with MIC of 2 mg/l against M. aurum.     

Akt regulates COX-2 mRNA and protein expression in mutated-PTEN human endometrial cancer cells

In human endometrial cancer, the fourth most common cancer in women, tumor suppressor phosphatase tensin homologue (PTEN) is frequently mutated. In the presence of a mutated PTEN protein, Akt phosphorylation levels are increased leading to the activation of this survival pathway. Numerous studies indicated that COX-2 is inappropriately induced and up-regulated in a number of malignant cancer cells. COX-2 plays an important role in tumor cell biology, taking part actively in angiogenesis particularly via the production of prostaglandin E2 (PGE2). The present study was undertaken to determine the involvement of PI 3-K/Akt pathway in the regulation of COXs expression and PGE2 synthesis. Three different human endometrial cancer cell lines known to have wild-type PTEN (HEC 1-A) or a mutated inactive PTEN protein (RL 95-2 and Ishikawa) were used for these studies. Results showed that Akt phosphorylation was high in mutated PTEN cells. RT-PCR studies revealed that Akt1 and Akt2 were the regulated forms whereas Akt3 mRNA was nearly undetectable. COX-2 mRNA expression and protein levels were high in these cells compared to wild-type PTEN cells as demonstrated by RT-PCR and Western analysis respectively. PGE2 production was higher in mutated-PTEN expressing phospho-Akt and COX-2 compared to wild-type PTEN cells. Inhibition of PI 3-K with Wortmannin and LY294002 blocked Akt phosphorylation and inhibited expression of COX-2 in mutated-PTEN cells. Inhibition of Akt phosphorylation with specific PI 3-K inhibitors and down-regulation of COX-2 increased apoptosis in human endometrial cancer cells. Likewise, transfection of mutated-PTEN cells with a dominant negative Akt vector, resulted in COX-2 down-regulation and activation of apoptosis, as demonstrated by Hoechst nuclear staining. On the opposite, activation of Akt using a constitutively active expression vector, resulted in the up-regulation of COX-2 protein expression. Specific inhibition of COX-2 with NS-398 induced apoptosis in COX-2 expressing human endometrial cancer cells. It is concluded that the PI 3-K/Akt survival pathway is involved in the regulation of COX-2 and PGE2 synthesis in human endometrial cancer cells.     

The projection from auditory cortex to cochlear nucleus in guinea pigs: an in vivo anatomical and in vitro electrophysiological study

Previous anatomical experiments have demonstrated the existence of a direct, bilateral projection from the auditory cortex (AC) to the cochlear nucleus (CN). However, the precise relationship between the origin of the projection in the AC and the distribution of axon terminals in the CN is not known. Moreover, the influence of this projection on CN principal cells has not been studied before. The aim of the present study was two-fold. First, to extend the anatomical data by tracing anterogradely the distribution of cortical axons in the CN by means of restricted injections of biotinylated dextran amine (BDA) in physiologically characterized sites in the AC. Second, in an in vitro isolated whole brain preparation (IWB), to assess the effect of electrical stimulation of the AC on CN principal cells from which intracellular recordings were derived. BDA injections in the tonotopically organized primary auditory cortex and dorsocaudal auditory field at high and low best frequency (BF) sites resulted in a consistent axonal labeling in the ipsilateral CN of all injected animals. In addition, fewer labeled terminals were observed in the contralateral CN, but only in the animals subjected to injections in low BF region. The axon terminal fields consisting of boutons en passant or terminaux were found in the superficial granule cell layer and, to a smaller extent, in the three CN subdivisions. No axonal labeling was seen in the CN as result of BDA injection in the secondary auditory area (dorsocaudal belt). In the IWB, the effects of ipsilateral AC stimulation were tested in a population of 52 intracellulary recorded and stained CN principal neurons, distributed in the three CN subdivisions. Stimulation of the AC evoked slow late excitatory postsynaptic potentials (EPSPs) in only two cells located in the dorsal CN. The EPSPs were induced in a giant and a pyramidal cell at latencies of 20 ms and 33 ms, respectively, suggesting involvement of polysynaptic circuits. These findings are consistent with anatomical data showing sparse projections from the AC to the CN and indicate a limited modulatory action of the AC on CN principal cells.     

Soluble intercellular adhesion molecule 1 in umbilical cord serum: potential for the diagnosis of neonatal infections

OBJECTIVE: To evaluate the diagnostic relevance to neonatal infections of the soluble intercellular adhesion molecule 1 (sICAM-1) cord serum level. METHODS: The case-control study included 66 term newborn infants with and without risk factors for neonatal infections. Cord blood serum determinations of white blood cell count, C-reactive protein, fibrinogen, and sICAM-1 were systematically performed associated with bacterial cultures from placenta, ears, and gastric fluids. RESULTS: 6 of 33 infants (18.2%) with risk factors were infected, and 13 (39.4%) were colonized. Two infants included in the group without infection risk factors (n = 33) were colonized. No difference in sICAM-1 cord serum levels was found according to the presence of premature rupture of membrane, fetal tachycardia >160 bpm, meconial amniotic fluid, and duration of labour >10 h. No difference in sICAM-1 was noted between infected and non-infected infants. The cord serum levels of sICAM-1 were significantly higher in infants after forceps extraction (p = 0.01). A correlation was observed between sICAM-1 and C-reactive protein cord serum levels (p = 0.004, r = 0.371) and between sICAM-1 level and neutrophil count (p = 0.01, r = 0.489). CONCLUSIONS: Our results suggest that cord serum sICAM-1 determinations have no diagnostic relevance to neonatal infection. The increase of sICAM-1 cord serum levels in infants after forceps extraction suggests its potential to evaluate cerebral trauma or hypoxia.     

Complications of urethral sling procedures

PURPOSE OF REVIEW: To review the current literature on complications of suburethral slings used to treat stress urinary incontinence in the female. RECENT FINDINGS: The surgical treatment of female urinary incontinence has changed considerably since the development of the tension-free vaginal tape procedure, introduced by Ulmsten in 1995. As the follow-up for the first studies is now more than 5 years, the 'long-term' results of the technique can be evaluated. Furthermore, now that the learning phase has been completed and the technique can be considered to be well mastered, it is interesting to review the complications inherent in this technique, their frequency, including those rarer complications that are sometimes associated with severe morbidity, and to consider the ways in which these complications can be prevented or treated. The development of the tension-free vaginal tape procedure has not prevented the development of other types of suburethral sling, but on the contrary, has promoted the development of these alternatives by the use of various sling insertion techniques, and especially various types of materials. There has even been a renewed interest in materials that have been known for a long time (heterologous and autologous materials) in some recent papers, and new synthetic suburethral slings have been proposed with the objectives of combining low morbidity, safety and efficacy. SUMMARY: Monofilament polypropylene meshes can be used safely to perform suburethral slings and seems to be the most suitable material in this indication according to the existing literature.     

Conjugated linoleic acid content in breast adipose tissue of breast cancer patients and the risk of metastasis

The association between the level of conjugated linoleic acid (CLA) in breast adipose tissue at the time of diagnosis and the subsequent development of metastasis was examined in a cohort of 209 patients presenting with an initially localized breast cancer. CLA level in breast adipose tissue was used as a qualitative biomarker of its past dietary intake. Biopsies of adipose tissue were obtained at the time of initial surgery. A CLA-enriched fraction was prepared by high performance liquid chromatography and CLA measured as a percentage of total fatty acids, using capillary gas chromatography. Mean CLA level was low (0.44% of total fatty acids) and the range between patients was narrow (0.19-0.85). With a median follow-up time of 7.5 yr, 45 patients developed metastases. A Cox proportional hazard regression model was used to identify prognostic factors. We did not find any significant association between CLA level in adipose fat and either the prognostic factor (tumor size, nodal status, histoprognostic grade, mitotic index, and estrogen or progesterone receptors) or the risk of metastasis or death. We concluded that CLA are unlikely to be involved in survivorship. However, the hypothesis that a higher intake of CLA might have a protective effect on the risk of metastasis cannot be ruled out from these data, since the level of CLA in breast cancer patients' adipose tissue is likely to be too low and the range of CLA distribution too narrow for any protection to be detectable.     

Are psychotic symptoms related to vagus nerve stimulation in epilepsy patients?

Four patients with refractory epilepsy presented with psychotic symptoms following treatment with vagus nerve stimulation (VNS) to control seizures. Besides its anti-epileptic effect VNS has been shown to have an effect on various cognitive and behavioural functions. VNS is known to increase alertness and reduce sedation, which is independent from seizure control. VNS has also been shown to positively affect cognition and to exert strong antidepressant effects. Co-morbidity in epilepsy often comprises psychiatric illnesses. Increased psychiatric symptoms have mainly been described in association with successful outcome following epilepsy surgery as a result of 'forced normalisation'. Different hypotheses on the underlying aetiology of VNS-induced psychotic symptoms other than the previously described 'forced normalisation' are discussed.