Posttraumatic stress disorder symptoms after bone marrow transplantation for breast cancer

Hormonal treatments which have an androgenic effect have the potential to cause vocal changes. The changes in vocal fold structure and voice quality are considered to be irreversible. To date, studies have documented subjective vocal changes or documented single cases without detailed, baseline voice assessments. The impact on laryngeal function of women taking these androgenic treatments requires further detailed, objective assessment. The need for increased awareness of the actions of androgenic hormones on womens' voices, and the benefits of a thorough voice assessment are discussed.     

Environment and health: an analysis of intra-urban differentials in the city of S?o Paulo, Brazil

A field study undertaken in the city of S. Paulo is presented as part of the project Environment and Health in Developing Countries: An Analysis of Intra-Urban Differentials Using Existing Data financed by the Ministry of Foreign Affairs of the United Kingdom with academic support from the London School of Hygiene and Tropical Medicine (LSHTM). The research aim was to fill in the gaps in the information needed to establish associations between mortality, urbanization and the environment. Statistics were produced by means of existing data collected by city departments, research carried out by universities and census data. Data quality was assessed taking into consideration data coverage, accuracy, and sensibility to pinpoint deprived areas in the city of S. Paulo. Socioeconomic data were used to create a composite index for districts and subdistrict in order to form four socioeconomic zones. Mortality differentials between the zones by five broad age groups (0-4, 5-14, 15-44, 45-64 e 65+) and four ICD chapters (circulatory, respiratory, infectious and parasitic and external causes) are presented. The zoning used showed that 43.8% of S. Paulo residents live in areas under the worst socioeconomic conditions. Health data demonstrated that people living in this areas had higher rates of mortality then those living in the areas with the best conditions. Finally, excess mortality data are analyzed and suggested as a good method for allocating health resources.     

Tissue reactions to bacteria-challenged implantable leads with enhanced infection resistance

Tissue reactions to implantable pacemaker leads were investigated in an early infection model in rabbits. Both standard leads and surface-modified leads were used. The surface modification technique was applied to achieve controlled release of the antibiotic gentamicin. The insulating polyurethane tubing material of the leads was provided with an acrylic acid/acrylamide copolymer surface graft and then loaded with gentamicin. Implantation periods varied from day 4, to week 3 1/2, to week 10. We investigated tissue reactions in the absence of an infectious challenge and also the efficacy of surface-modified leads in preventing infection after challenge with Staphylococcus aureus was evaluated. It was demonstrated that the applied surface modification did not induce adverse effects although during early postimplantation an increase in infiltration of granulocytes and macrophages and wound fluid and fibrin deposition were observed. After bacterial challenge, standard leads were heavily infected at each explantation period, denoted by abscesses, cellular debris, and bacterial colonies. In contrast, little or no infection was observed, either macroscopically or by bacterial cultures, with the surface-modified leads. Microscopy showed little evidence of the bacterial challenge, and that primarily at day 4. It was concluded that the applied surface modification demonstrated enhanced infection resistance and thus represents a sound approach to the battle against infectious complications with biomaterials.     

Comparison of diarrhea induced by ingestion of fructooligosaccharide Idolax and disaccharide lactulose: role of osmolarity versus fermentation of malabsorbed carbohydrate

Whether carbohydrate malabsorption causes diarrhea probably depends on the balance between the osmotic force of the carbohydrate and the compensatory capacity of the colon to dispose of the carbohydrate by bacterial fermentation. The present study evaluated the specific role of the osmolarity by comparing the severity of diarrhea after ingestion of two nonabsorbable carbohydrates, the fructooligosaccharide Idolax and the disaccharide lactulose. Both carbohydrates are readily fermented by the colonic flora but differ in osmolarity, the osmotic force being twice as high for lactulose as for Idolax. Twelve subjects were given increasing doses (0, 20, 40, 80, 160 g/d) of Idolax and lactulose in a crossover design. Every dose level was administered for three days with intervals of one week. Stools were collected on the third day to determine 24-hr volume, concentrations of short-chain fatty acids, L- and D-lactate, residues of Idolax or lactulose, sodium, potassium, pH, osmolarity, and in vitro productions of organic acids. Measured by short-chain fatty acid and lactate formation in a fecal incubation system, the fermentation of Idolax and lactulose was identical and very rapid compared with a range of reference carbohydrates. A laxative effect of both Idolax and lactulose was demonstrated. The increment in fecal volume as a function of the dose administered was twice as high for lactulose (slope of the regression line = 7.3, r = 0.64, P< 10(-5)) as for Idolax (slope = 3.7, r = 0.51, P<10(-3)), i.e., isosmolar doses of lactulose and Idolax had the same effect on fecal volume. The variation in fecal volume was substantial (lactulose 80 g/day: 110-1360 g/day; Idolax 160 g/day: 130-1440 g/day). High responders had earlier and larger fecal excretions of the saccharide compared with low-responders. Fecal volume in carbohydrate-induced diarrhea is proportional to the osmotic force of the malabsorbed saccharide, even though all or the majority of the saccharide is degraded by colonic bacteria. The capacity to modify the diarrhea varies considerably from person to person and is associated with colonic saccharide disposal, whereas the variation in response to isosmolar amounts of different saccharides is small within the same individual.     

The principal rapamycin-sensitive p70(s6k) phosphorylation sites, T-229 and T-389, are differentially regulated by rapamycin-insensitive kinase kinases

Mitogen-induced activation of p70(s6k) is associated with the phosphorylation of specific sites which are negatively affected by the immunosuppressant rapamycin, the fungal metabolite wortmannin, and the methylxanthine SQ20006. Recent reports have focused on the role of the amino terminus of the p85(s6k) isoform in mediating kinase activity, with the observation that amino-terminal truncation mutants are activated in the presence of rapamycin while retaining their sensitivity to wortmannin. Here we show that the effects of previously described amino- and carboxy-terminal truncations on kinase activity are ultimately reflected in the phosphorylation state of the enzyme. Mutation of the principal rapamycin-targeted phosphorylation site, T-389, to an acidic residue generates a form of the kinase which is as resistant to wortmannin or SQ20006 as it is to rapamycin, consistent with the previous observation that T-389 was a common target of all three inhibitors. Truncation of the first 54 residues of the amino terminus blocks the serum-induced phosphorylation of three rapamycin-sensitive sites, T-229 in the activation loop and T-389 and S-404 in the linker region. This correlates with a severe reduction in the ability of the kinase to be activated by serum. However, loss of mitogen activation conferred by the removal of the amino terminus is reversed by additional truncation of the carboxy-terminal domain, with the resulting mutant demonstrating phosphorylation of the remaining two rapamycin-sensitive sites, T-229 and T-389. In this double-truncation mutant, phosphorylation of T-229 occurs in the basal state, whereas mitogen stimulation is required to induce acute upregulation of T-389 phosphorylation. The phosphorylation of both sites proceeds unimpaired in the presence of rapamycin, indicating that the kinases responsible for the phosphorylation of these sites are not inhibited by the macrolide. In contrast, activation of the double-truncation mutant is blocked in the presence of wortmannin or SQ20006, and these agents completely block the phosphorylation of T-389 while having only a marginal effect on T-229 phosphorylation. When the T-389 site is mutated to an acidic residue in the double-truncation background, the activation of the resulting mutant is insensitive to the wortmannin and SQ20006 block, but interestingly, the mutant is activated to a significantly greater level than a control in the presence of rapamycin. These data are consistent with the hypothesis that T-389 is the principal regulatory phosphorylation site, which, in combination with hyperphosphorylation of the autoinhibitory domain S/TP sites, is acutely regulated by external effectors, whereas T-229 phosphorylation is regulated primarily by internal mechanisms.     

Localization of Chlamydia trachomatis heat shock proteins 60 and 70 during infection of a human endometrial epithelial cell line in vitro

Unlike chlamydial lipopolysaccharide, which is released from the developing inclusion to the surface of infected genital epithelial cells, both Chlamydia trachomatis heat shock protein (hsp) 60 and 70 antigens remained confined within the inclusion during the course of the chlamydial developmental cycle. Exposure of the infected cells to penicillin to induce a persistent infection or to a lipophilic microbicide did not potentiate secretion or exocytosis of the chlamydial hsp.     

Effect of aluminum on cytoplasmic Ca2+ homeostasis in root hairs of Arabidopsis thaliana (L.)

Aluminum inhibition of root growth is a major world agricultural problem where the cause of toxicity has been linked to changes in cellular calcium homeostasis. Therefore, the effect of aluminum ions (Al) on changes in cytoplasmic free calcium concentration ([Ca2+]c) was followed in root hairs of wild-type, Al-sensitive and Al-resistant mutants of Arabidopsis thaliana (L.) Heynh. Generally, Al exposure resulted in prolonged elevations in tip-localized [Ca2+]c in both wild-type and Al-sensitive root hairs. However, these Al-induced increases in [Ca2+]c were not tightly correlated with growth inhibition, occurring up to 15 min after Al had induced growth to stop. Also, in 32% of root hairs examined growth stopped without a detectable change in [Ca2+]c. In contrast, Al-resistant mutants showed little growth inhibition in response to AlCl3 exposure and in no case was a change in [Ca2+]c observed. Of the other externally applied stresses tested (oxidative and mechanical stress), both were found to inhibit root hair growth, but only oxidative stress (H2O2, 10 microM) caused a prolonged rise in [Ca2+]c similar to that induced by Al. Again this increase occurred after growth had been inhibited. The lack of a tight correlation between Al exposure, growth inhibition and altered [Ca2+]c dynamics suggests that although exposure of root hairs to toxic levels of Al causes an alteration in cellular Ca2+ homeostasis, this may not be a required event for Al toxicity. The elevation in [Ca2+]c induced by Al also strongly suggests that the phytotoxic action of Al in root hairs is not through blockage of Ca2(+)-permeable channels required for Ca2+ influx into the cytoplasm.     

Pathologic features from prostate needle biopsy and prognosis after I-125 brachytherapy

To evaluate the role of detailed pathologic features in predicting outcome for early-stage prostate cancer treated with I-125 brachytherapy. The pretreatment biopsy slides of 103 patients with T1/T2 and Gleason scores of 4-7 prostatic carcinoma, which was treated by transperineal I-125 implantation, were reviewed retrospectively by a single pathologist (P.B.G.). Biochemical tumor control rates [prostate-specific antigen (PSA) below 1.0] were correlated with pretreatment PSA, Gleason score, the amount of tumor in the biopsy samples, and the presence of perineural invasion. In Cox proportional-hazard, multivariate analysis, the strongest predictors of failure were pretreatment PSA above 10 ng/ml (P = 0.013) and the length of the biopsy specimen replaced by tumor (P = 0.15). The percent of biopsy tissue replaced by tumor (P = 0. 74), perineural invasion (P = 0.78), and Gleason score (P = 0.66) were less predictive of prognosis. It was concluded that pretreatment PSA is the strongest predictor of biochemical failure. Detailed assessment of pathological features on needle biopsy added little prognostic information beyond that of pretreatment PSA alone. Like all other prognostic parameters for prostate cancer, there is considerable overlap in pathologic features between those patients who will or will not be controlled biochemically.