Early production of table olives at a mid-7th millennium BP submerged site off the Carmel coast (Israel).

We present here the earliest evidence for large-scale table olive production from the mid-7th millennium BP inundated site of Hishuley Carmel on the northern Mediterranean coast of Israel. Olive pit size and fragmentation patterns, pollen as well as the architecture of installations associated with pits from this site, were compared to finds from the nearby and slightly earlier submerged Kfar Samir site. Results indicate that at Kfar Samir olive oil was extracted, while at Hishuley Carmel the data showed that large quantities of table olives, the oldest reported to date, were prepared. This process was most probably facilitated by the site's proximity to the Mediterranean Sea, which served as a source of both sea water and salt required for debittering/pickling/salting the fruit, as experimentally demonstrated in this study. Comparison of pit morphometry from modern cultivars, wild-growing trees and the archaeological sites, intimates that in pit morphology the ancient pits resemble wild olives, but we cannot totally exclude the possibility that they derive from early cultivated trees. Our findings demonstrate that in this region, olive oil production may have predated table olive preparation, with each development serving as a milestone in the early exploitation of the olive.

Comparison of sporadic and familial behavioral variant frontotemporal dementia (FTD) in a North American cohort.

INTRODUCTION: Behavioral variant frontotemporal dementia (bvFTD) may present sporadically or due to an autosomal dominant mutation. Characterization of both forms will improve understanding of the generalizability of assessments and treatments. METHODS: A total of 135 sporadic (s-bvFTD; mean age 63.3 years; 34% female) and 99 familial (f-bvFTD; mean age 59.9; 48% female) bvFTD participants were identified. f-bvFTD cases included 43 with known or presumed chromosome 9 open reading frame 72 (C9orf72) gene expansions, 28 with known or presumed microtubule-associated protein tau (MAPT) mutations, 14 with known progranulin (GRN) mutations, and 14 with a strong family history of FTD but no identified mutation. RESULTS: Participants with f-bvFTD were younger and had earlier age at onset. s-bvFTD had higher total Neuropsychiatric Inventory Questionnaire (NPI-Q) scores due to more frequent endorsement of depression and irritability. DISCUSSION: f-bvFTD and s-bvFTD cases are clinically similar, suggesting the generalizability of novel biomarkers, therapies, and clinical tools developed in either form to the other.

Intra-amniotic digoxin for feticide between 21 and 30 weeks of gestation: a prospective study.

OBJECTIVE: Intra-amniotic injection of digoxin is a well-known method for feticide before inducing a termination of pregnancy (TOP) at 17-24 weeks of gestation. Information on its effectiveness when administered after 24 weeks of gestation is limited. This study evaluated the efficacy of intra-amniotic digoxin injection for inducing fetal demise within 18-24 hours, at 21-30 weeks of gestation, and its safety. DESIGN: Prospective cohort study. SETTING: Tertiary university medical centre. POPULATION: Women at 21-30 weeks of gestation with a singleton pregnancy, admitted for TOP. METHODS: Intra-amniotic injection of 2 mg of digoxin was performed 1 day before medical TOP. Fetal heart activity was evaluated by ultrasound for 18-24 hours after the injection. Serum digoxin level and maternal electrocardiogram (ECG) were evaluated 6, 10, and 20 hours after injection. MAIN OUTCOME MEASURE: Frequency of successful fetal demise. RESULTS: Fifty-nine women participated in the study. The mean gestational age was 24+2  weeks (range 21+0 -30+0 ), with 29 (49.2%) beyond 24+0  weeks of gestation. Fetal cardiac activity arrest was achieved in 55/59 cases (93.2%). Normal maternal ECG recordings were noted in all cases. Mean serum digoxin levels 6 and 10 hours after injection were in the therapeutic range (1.3 ± 0.7 ng/l and 1.24 ± 0.49 ng/l, respectively) and below the toxic level (2 ng/l). Extramural delivery following digoxin did not occur. There were no cases of chorioamnionitis. CONCLUSION: Intra-amniotic digoxin for feticide at 21-30 weeks of gestation in a singleton pregnancy appears effective and safe before TOP at advanced gestational ages. TWEETABLE ABSTRACT: This study shows that feticide by intra-amniotic digoxin injection at 21-30 weeks of gestation appears effective and safe.

Cochlear implant and congenital cholesteatoma.

BACKGROUND: The occurence of cholesteatoma and cochlear implant is rare. Secondary cholesteatomas may develop as a result of cochlear implant surgery. Primarily acquired cholesteatoma is not typically associated with congenital sensorineural hearing loss or cochlear implant in children. The occurrence of congenital cholesteatoma during cochlear implant surgery has never been reported before, partly because all patients are preoperatively submitted to imaging studies which can theoretically exclude the disease. CASE PRESENTATION: We have reported a rare case of congenital cholesteatoma, found during sequential second side cochlear implantation in a 3-year-old child. The child underwent a computed tomography (CT) scan and magnetic resonance imaging (MRI) at 12 months of age, before the first cochlear implant surgery, which excluded middle ear pathology. The mass was removed as an intact pearl, without visible or microscopic violation of the cholesteatoma capsule. All the areas where middle ear structures were touching the cholesteatoma were vaporized with a laser and the cochlear implant was inserted uneventfully. Further follow-up excluded residual disease. CONCLUSION: We believe that primary, single stage placement of a cochlear implant (CI) with simultaneous removal of the congenital cholesteatoma can be performed safely. However, to prevent recurrence, the capsule of the cholesteatoma must not be damaged and complete laser ablation of the surface, where suspicious epithelial cells could remain, is recommended. In our opinion, cholesteatoma removal and cochlear implantation should be staged if these conditions are not met, and/or the disease is at a more advanced stage. It is suspected, that the incidence of congenital cholesteatoma in pediatric CI candidates is much higher that in average pediatric population.

[MORPHO-FUNCTIONAL CHARACTERISTICS OF KIMMERLE ANOMALY].

The study material included 105 isolated bone preparations of the atlas, 100 radiographs of the cervical region of the spine, 650 spiral computed tomography (SCT) scans and 224 protocols of duplex ultrasound scanning of extracranial portions of brachiocephalic arteries and transcranial duplex scanning. Kimmerle anomaly was detected in 18% of cases in the bone material, in 17% of the cases of SCT and in 15% of cases during radiological examination. The anomaly more often is unilateral, rarely--bilateral; it may be located medially or laterally, while the vertebral artery canal more frequently is closed, less commonly--open. Among the patients with Kimmerle anomaly, hemodynamically significant asymmetry of blood flow velocity in the vertebral arteries was detected in 78.5% of cases. Thus, the most important method of Kimmerle anomaly detection is SCT with contrast-enhanced artery imaging. However, each of the research methods successively. Each of research methods used consistently allows to obtain information both on anatomical variability of atlas developmental abnormalities (morphological characteristics) and on possible functional disorders, morphological basis of which is Kimmerle anomaly.

First trimester human placental factors induce breast cancer cell autophagy.

Placental factors, progesterone included, facilitate breast cancer cell line (BCCL) motility and thus may contribute to the advanced breast cancer found during pregnancy. Cancer and placental implantations are similar; the last is accompanied by extravillous trophoblast cell invasion and autophagy which are interlinked. We aimed to analyze the effect of first trimester human placenta on BCCL autophagy. BCCLs (MCF-7/T47D) were cultured with placental explants (60 h) or placental supernatants (24 h). Following cultures, BCCLs were sorted out for RNA/protein extraction. RNA served for microarray/qPCR (BNIP3) and protein for Western blot (HIF1α, LC3BII) analyses. Inhibitors were added to the placenta-MCF-7 coculture or placental supernatants (autophagy inhibitor-3MA, progesterone receptor (PR) inhibitor-RU486, and HIF1α inhibitor-Vitexin) in order to evaluate their effects on BCCL motility and LC3BII/HIF1α expression. LC3BII (an autophagy marker) expression was elevated in BCCLs following placental explant coculture and exposure to placental supernatants. The autophagy inhibitor (3MA) repressed the placenta-induced MCF-7/T47D migration, establishing a connection between BCCL autophagy and migration. Microarray analysis of MCF-7 following placenta-MCF-7 coculture showed that "HIF1α pathway," a known autophagy facilitator, was significantly manipulated. Indeed, placental factors elevated HIF1α and its target BNIP3 in the BCCLs, verifying array results. Lastly, PR inhibitor reduced HIF1α expression and both PR and HIF1α inhibitors reduced MCF-7 LC3BII expression and motility, suggesting involvement of the PR-HIF1α axis in the autophagy process. Placental factors induced BCCL autophagy that is interlinked to their motility. This suggests that autophagy-related molecules may serve as targets for therapy in pregnancy-associated breast cancer.

Functional and physical outcomes following use of a flexible CO2 laser fiber and bipolar electrocautery in close proximity to the rat sciatic nerve with correlation to an in vitro thermal profile model.

This study compared functional and physical collateral damage to a nerve when operating a Codman MALIS Bipolar Electrosurgical System CMC-III or a CO2 laser coupled to a laser, with correlation to an in vitro model of heating profiles created by the devices in thermochromic ink agarose. Functional damage of the rat sciatic nerve after operating the MALIS or CO2 laser at various power settings and proximities to the nerve was measured by electrically evoked nerve action potentials, and histology of the nerve was used to assess physical damage. Thermochromic ink dissolved in agarose was used to model the spatial and temporal profile of the collateral heating zone of the electrosurgical system and the laser ablation cone. We found that this laser can be operated at 2 W directly above the nerve with minimal damage, while power settings of 5 W and 10 W resulted in acute functional and physical nerve damage, correlating with the maximal heating cone in the thermochromic ink model. MALIS settings up to 40 (11 W) did not result in major functional or physical nerve damage until the nerve was between the forceps tips, correlating with the hottest zone, localized discretely between the tips.

Ureteroscopy and laser lithotripsy: technologic advancements.

Ureteroscopic lithotripsy has evolved since the first reported cases employing rigid rod-lens endoscopes and stiff ultrasonic lithotrites. Fiber optics facilitated rigid endoscope miniaturization and the development of a steerable, deflectable flexible ureteroscopes. Over 30 years of technical innovations culminating in digital imagers and powerful, precise laser lithotrites, complimented by progressive endoscopic techniques have produced efficient endoscopic therapies with minimal morbidity and commonly performed in an outpatient setting.

Variation in quantity and composition of cuticular hydrocarbons in the scorpion Buthus occitanus (Buthidae) in response to acute exposure to desiccation stress.

Scorpions exhibit some of the lowest recorded water loss rates among terrestrial arthropods. Evaporative water loss to the surrounding environment occurs mainly through the integument, and thus its resistance to water loss has paramount significance for the ability of scorpions to tolerate extremely dry habitats. Cuticular hydrocarbons (HCs) deposited on the outer epicuticle play an important role in determining cuticular waterproofing, and seasonal variation in both cuticular HC quantity and composition has been shown to correlate with water loss rates. Precursor incorporation rates into cuticle HCs have been observed to be extremely low in scorpions compared with insects. We therefore used adult male Buthus occitanus (Buthidae) in order to test HC profile plasticity during acute exposure to 14 d and 28 d of experimental desiccation. Cuticular HC profile of hydrated scorpions was similar to that reported for several other scorpion species, consisting of similar fractions of n-alkanes and branched alkanes, with no evidence for unsaturation. Most abundant of the n-alkanes were n-heptacosane (C27; 19±2% of total HCs), n-nonacosane (C29; 16±1%) and n-hentriacontane (C31; 11±1%). Exposure to desiccation stress resulted in a significant increase in the total amount of extracted HCs, and in the relative abundance of branched alkanes at the expense of n-alkanes. Together with an increase in HC chain lengths, these changes mimic previously-reported seasonal variation among freshly-collected specimens. This indicates that scorpions respond to water shortage by regulating the properties of their passive integumental barrier to water loss.

A study of van der Waals complexes of 1,2-dichloroethane in paraffin oil by FTIR spectroscopy and ab initio calculations.

Weak molecular interactions of 1,2-dichloroethane dissolved in paraffin oil were investigated by FTIR spectroscopy. Occurrence of isosbestic points in the spectra along with the factor analysis showed that DCE⋯DCE dimers are formed in solutions at DCE concentrations between 7 and 15 vol.%. It was found that both trans and gauche conformers are involved in the complexation, forming a tg-dimer. From the spectra collected at 200-222 K, the complexation enthalpy was determined: -4.2±0.4 kcal mol(-1). The equilibrium geometry of tg-dimer and the vibrational frequencies were determined from the density functional calculations performed at B3LYP/6-311++G(d,p) and 6-31G(d,p) levels. The C-C bonds of the two molecules involved in tg-dimers were found to be oriented nearly perpendicular to each other. The complexation energy calculated using 6-31G(d,p) and 6-311++G(d,p) basis sets was found to be -1.59 and -1.52 kcal mol(-1), respectively.

The effect of heat shock protein 27 on extravillous trophoblast differentiation and on eukaryotic translation initiation factor 4E expression.

Heat shock protein (HSP27) is expressed in human placentae. Previously, we showed that HSP27 is expressed in the villous cell column of first trimester placental explants and in extravillous trophoblast (EVT) cells. EVT differentiation is accompanied by increased motility, matrix metalloproteinase (MMP) activity, decreased proliferation and expression of specific markers such as HLAG and CD9. HSP27 regulates cell apoptosis, migration, protein stability and the availability of eukaryotic translation initiation factors, such as eukaryotic translation initiation factor 4E (eIF4E). eIF4E supports trophoblast cell proliferation and survival. We wanted to explore the effect of HSP27 silencing on trophoblast cell phenotype, EVT markers and eIF4E expression and regulators [4E-binding protein (4E-BP1) and MAP kinase-interacting kinase (MNK1)]. This study evaluated the effect of HSP27 siRNA on placental explant and HTR-8/SVneo migration, MMP activity/mRNA, cell death, cell cycle, HLAG/CD9 levels, and eIF4E and its regulators' total and phosphorylated levels. Furthermore, we evaluated HSP27 levels in placentae exposed to ribavirin, which triggers EVT differentiation. We found that HSP27 silencing increased cell death in HTR-8/SVneo and placental explants. Furthermore, it reduced HTR-8/SVneo migration and EVT outgrowth from the explants (P < 0.05), MMP2 activity and expression of EVT markers HLAG and CD9 (in placental explants and HTR-8/SVneo, respectively, P < 0.05). Induction of EVT differentiation by ribavirin elevated HSP27 levels. Finally, HSP27 silencing in both HTR-8/SVneo and placental explants reduced eIF4E levels (33 and 28%, respectively, P < 0.05) and the levels of its regulators 4E-BP1 and MNK1 (37 and 32%, respectively, done on HTR-8/SVneo only), but not their phosphorylated forms. Altogether, our results suggest that HSP27 contributes to EVT cell differentiation.

Successful response to docetaxel treatment in recurrent ovarian granulosa cell tumor: a case report.

BACKGROUND: Ovarian granulosa cell tumor (GCT) is primarily treated surgically. Treatment for advanced or recurrent disease includes primary or adjuvant chemotherapy. Data about the efficacy of treatment with paclitaxel are limited, without data about the role of docetaxel in treating recurrent GCT. CASE: A 68-year-old patient with Stage IA ovarian GCT diagnosed ten years earlier, presented with a third episode of recurrent disease. Following the first event of recurrent disease, she underwent a second laparotomy followed by BEP chemotherapy. Because of new liver masses, she was treated with paclitaxel, with complete response. Following diagnosis of new liver lesions, third-line chemotherapy with docetaxel was initiated, resulting in stable disease and a PFI of 24 months. CONCLUSION: Docetaxel might be a good alternative for treating recurrent GCT.

The involvement of eukaryotic translation initiation factor 4E in extravillous trophoblast cell function.

UNLABELLED: Extravillous trophoblast cells (EVT) are major players in placental implantation. They differentiate in the villous cell column, invade to the uterus and remodel the uterine spiral arteries. Trophoblast and tumor cells have similar invasion mechanisms, share similar biochemical mediators (e.g. c-myc, MMP9) and growth-factors (e.g. VEGF). The mRNA of these proteins has extremely structured 5-UTR and their translation is highly dependent on eukaryotic-translation-initiation-factor-4E (eIF4E). Cancer cells have elevated eIF4E and are more vulnerable to its silencing than normal cells. We speculated that like cancer, trophoblast function is highly eIF4E dependent. OBJECTIVE: Analyze eIF4E involvement in EVT differentiation and function. STUDY DESIGN: EIF4E levels were assessed in first-trimester human placentae and in placental explants before and after EVT differentiation. The effect of eIF4E knockdown (siRNA, ribavirin) on the phenotype of placental explant and EVT cell lines (HTR-8/SVNEO) was evaluated. Tested parameters included eIF4E and its target levels, migration, invasion, cell death, cell cycle and cell count. RESULTS: High eIF4E levels were found in cytotrophoblast and especially EVT cells during their differentiation in the villi, compared to other placental cell types. EIF4E silencing increased cell death and cell cycle arrest in placental explants and HTR-8/SVNEO cells. Although it induced EVT outgrowth in the placental explants, it reduced HTR-8/SVNEO motility, reflecting the importance of using ex vivo models that include an intact placental microenvironment in its original architecture. CONCLUSIONS: Our results suggest that eIF4E prevents final EVT differentiation and supports placental cell proliferation and survival. A balance between cell proliferation and differentiation is crucial for placental development and implantation.

Conformational mobility of small molecules in glass-forming solutions studied by FTIR spectroscopy.

Small molecules with two or more stable conformations when embedded in a glass-forming liquid (matrix) serve the role of "conformational probes", i.e., their conformational transitions are used to follow local mobility in the matrix. In the present study, conformational probes were embedded in low-molecular-weight glass-forming liquids, and the molecular mobility was studied in a broad temperature range including the glass transition temperature (T(g)). Paraffin oil, dibutylphthalate, bis(2-ethylhexyl)phthalate and isopropylbenzene were used as glass-forming liquids while 1,2-dichloroethane, 1,2-diphenylethane, chlorocyclohexane and bromocyclohexane were used as conformational probes. For some of the matrix/probe systems, the conformational mobility was found to freeze-in at T(g), while for the others it froze-in at certain temperatures T(f)

Hormone-dependent placental manipulation of breast cancer cell migration.

BACKGROUND: Breast cancer during pregnancy is often more advanced than in non-pregnant women. Nevertheless, no case of metastasis inside the placenta has been reported. Previously, we showed that placental-explants eliminated breast cancer cells from their surroundings, due to cell-death and elevated migration. Our objective was to find the underlying mechanisms of these phenomena. METHODS AND RESULTS: Our model contained Michigan Cancer Foundation 7 (MCF7) or T47D cells co-cultured with and without human placental explants. Microarray analysis, validated by quantitative PCR, of MCF7 following their placental co-culture suggested activation of estrogen (E(2)) signaling. As extensive cross-talk exists between E(2) and progesterone, their involvement in mediating placental effects on breast cancer cells was tested. Indeed, addition of E(2) and progesterone receptor (ER and PR) inhibitors to the co-culture system reduced cancer cell motility, yet did not alter cell-cycle or death. E(2) and progesterone concentrations in placental media were found to be similar to those of early pregnancy blood levels. Interestingly, placental-breast cancer co-culture media contained lower progesterone (P < 0.05) and higher E(2) (200%, P < 0.05) levels than placentae cultured separately. Placental supernatant and E(2) and progesterone at placental levels were sufficient to increase MCF7 and T47D migration and invasion (P < 0.05), yet did not alter MCF7 cell-cycle or death. Furthermore, placental supernatant elevated p38 and Jun N-terminal kinase (JNK) phosphorylation in both cell lines (P < 0.05). Inhibitors of JNK, ER and PR reversed MCF7 and T47D motility induced by the placenta, suggesting their involvement. CONCLUSIONS: We suggest that E(2) and progesterone contribute to cell migration away from placental areas. We hypothesize that they may increase metastatic spread to other organs in pregnancy.

Spread of cochlear excitation during stimulation with pulsed infrared radiation: inferior colliculus measurements.

Infrared neural stimulation (INS) has received considerable attention over the last few years. It provides an alternative method to artificially stimulate neurons without electrical current or the introduction of exogenous chromophores. One of the primary benefits of INS could be the improved spatial selectivity when compared with electrical stimulation. In the present study, we have evaluated the spatial selectivity of INS in the acutely damaged cochlea of guinea pigs and compared it to stimulation with acoustic tone pips in normal-hearing animals. The radiation was delivered via a 200 µm diameter optical fiber, which was inserted through a cochleostomy into the scala tympani of the basal cochlear turn. The stimulated section along the cochlear spiral ganglion was estimated from the neural responses recorded from the central nucleus of the inferior colliculus (ICC). ICC responses were recorded in response to cochlear INS using a multichannel penetrating electrode array. Spatial tuning curves (STCs) were constructed from the responses. For INS, approximately 55% of the activation profiles showed a single maximum, ∼22% had two maxima and ∼13% had multiple maxima. The remaining 10% of the profiles occurred at the limits of the electrode array and could not be classified. The majority of ICC STCs indicated that the spread of activation evoked by optical stimuli is comparable to that produced by acoustic tone pips.

Breast cancer characteristics are modified by first trimester human placenta: in vitro co-culture study.

BACKGROUND: Pregnant women with breast cancer present with a more advanced disease compared with non-pregnant women. Nevertheless, breast cancer metastasis to the placenta is rare. Trophoblast/tumor implantations share the same biochemical mediators, while only the first is stringently controlled. We hypothesized that the same mechanisms that affect/restrain placental implantation may inhibit metastatic growth in the placenta. We aimed to analyze the effects of human placenta on breast cancer cells. METHODS: First trimester human placental explants were co-cultured with MCF-7/T47D-eGFP tagged cells. Following culture, placenta/cancer cells/both were fixed, paraffin embedded and sliced for immunohistochemical analysis or sorted by their eGFP expression for future analysis. The tested parameters were: proliferation (immunohistochemistry)/cell cycle (FACS), apoptosis (immunohistochemistry/FACS), cell count/adhesion/distribution around the placenta (cell sorter, visual observation and counting), matrix metalloproteinase activity (zymogram) and estrogen receptor (ER) expression (western blotting, immunohistochemistry). RESULTS: Reduced breast cancer cell numbers (45%↓, 48%↓ for MCF-7/T47D, respectively, P < 0.05) were observed near the placenta. The placenta elevated MCF-7 sub-G1 phase and modestly elevated apoptosis (3-17%↑ for T47D/MCF-7, respectively, P < 0.05). Our findings demonstrate breast cancer cell migration from the placenta as: (i) T47D/MCF-7 cells changed their morphology to that of motile cells; (ii) elevated MMPs activity was found in the co-culture; (iii) placental soluble factors detached breast cancer cells; and (4) the placenta reduced MCF-7/T47D cells' ER expression (a characteristic of motile cells). CONCLUSIONS: MCF-7/T47D cells are eliminated from the placental surroundings. Analyzing the causes of these phenomena may suggest biological pathways for this event and raise new therapeutic targets.

The vibrational spectra of 1,3-dithiane-1-oxide and 1,3-dithia-1-oxocyclohept-5-ene.

The IR spectra of 1,3-dithiane-1-oxide (I) and 1,3-dithia-1-oxocyclohept-5-ene (II) were recorded in solution, solid and liquid phase over 4000-400 cm(-1) spectral range. It was found that both (I) and (II) in liquid phase and solutions exist in two conformations: (I) chair-e (Ce) and chair-a (Ca) with equatorial and axial positions of the S=O bond, respectively, and (II) chair-e (Ce) and boat-e (Be). The intensity variations with temperature (300-180 K) of the bands 632 (Ca) and 644 cm(-1) (Ce) of (I) in acetone-d6 and the bands 482 (Be) and 448 cm(-1) (Ce) of (II) in melt were employed in Van't Hoff plot and gave the values DeltaH degrees (Ca-Ce) = 380 +/- 40 cal mol(-1) (I) and DeltaH degrees (Be-Ce) = 400 +/- 100 cal mol(-1) (II). Ab initio calculations were carried out with the Gaussian 98 program using the basis set 6-31G(d) for (I) and 6-311++G(d,p) for (II). The energy difference between Ca and Ce conformations for (I) and Be and Ce for (II) are in a good agreement with experimental results. Vibrational frequencies for both conformations (I) and (II) were calculated. After appropriate scaling a reasonably good agreement between the experimental and calculated wave numbers was obtained.

Prevalence and clinical correlates of bronchoreversibility in severe emphysema.

Chronic obstructive pulmonary disease (COPD) exhibits airflow obstruction that is not fully reversible. The importance of bronchoreversibility remains controversial. We hypothesised that an emphysematous phenotype of COPD would be associated with decreased bronchoreversibility. 544 patients randomised to the medical arm of the National Emphysema Treatment Trial formed the study group. Participants underwent multiple measurements of bronchoreversibility on a mean of four sessions over 1.91 yrs. They were also characterised by measures of symptoms, quality of life and quantitative measures of emphysema by computed tomography. Mean baseline forced expiratory volume in 1 s (FEV(1)) in this patient population is 24% predicted. 22.2% of patients demonstrated bronchoreversibility on one or more occasions using American Thoracic Society/European Respiratory Society criteria. Few patients (0.37%) had bronchoreversibility on all completed tests. Patients who demonstrated bronchoreversibility were more likely to be male, and have better lung function and less emphysema. 64% of patients demonstrated large (> or =400 mL) changes in forced vital capacity (FVC). In a severe emphysema population, bronchoreversibility as defined by change in FEV(1) is infrequent, varies over time, and is more common in males and those with less severe emphysema. Improvements in FVC, however, were demonstrated in the majority of patients.

Long-term glutamate supplementation failed to protect against peripheral neurotoxicity of paclitaxel.

Toxic peripheral neuropathy is still a significant limiting factor for chemotherapy with paclitaxel (PAC), although glutamate and its closely related amino acid glutamine were claimed to ameliorate PAC neurotoxicity. This pilot trial aimed to evaluate the role of glutamate supplementation for preventing PAC-induced peripheral neuropathy in a randomized, placebo-controlled, double-blinded clinical and electro-diagnostic study. Forty-three ovarian cancer patients were available for analysis following six cycles of the same PAC-containing regimen: 23 had been supplemented by glutamate all along the treatment period, at a daily dose of three times 500 mg (group G), and 20 had received a placebo (group P). Patients were evaluated by neurological examinations, questionnaires and sensory-motor nerve conduction studies. There was no significant difference in the frequency of signs or symptoms between the two groups although neurotoxicity symptoms presented mostly with lower scores of severity in group G. However, this difference reached statistical significance only with regard to reported pain sensation (P = 0.011). Also the frequency of abnormal electro-diagnostic findings showed similarity between the two groups (G: 7/23 = 30.4%; P: 6/20 = 30%). This pilot study leads to the conclusion that glutamate supplementation at the chosen regimen fails to protect against peripheral neurotoxicity of PAC.