Breast cancer surgery decreases serum brain-derived neurotrophic factor concentrations in middle aged women: relationship to the serum C-reactive protein concentration.

The aim of this study was to establish the effect of breast cancer surgery in middle aged women on the serum (s) and plasma (p) brain-derived neurotrophic factor concentrations [BDNF]s and [BDNF]p, respectively, in relation to the serum C-reactive protein [CRP]s concentration measured before and at 24 hours after surgery. Eighteen patients with recently diagnosed breast cancer (mean ± SE): age 49.1 ± 1.6 years, body mass 69.8 ± 2.2 kg, BMI 25.8 ± 0.8 kg m-2, participated in this study. The [BDNF]s before the surgery amounted to 25 523 ± 1 416 pg ml-1. At 24 h after the surgery it decreased to 21 551 ± 998 pg ml-1 (P = 0.004). This decrease was accompanied by a significant (P = 0.001) decrease in the platelet count (PLT) from 254.7 ± 12.2 k µl-1 before, to 228.8 ± 9.7 k µl-1 after the surgery. The [CRP]s increased from 3.59 ± 0.79 mg l-1 before to 25.04 ± 4.65 mg l-1 after the surgery (P = 0.002). A significant positive correlation was found between the [BDNF]s and the PLT both before (P = 0.003) as well as after the surgery (P = 0.027). Moreover, a significant positive correlation (P = 0.046) was found between [BDNF]s and the [CRP] s before the surgery. At 24 h after the surgery the [BDNF]s and the [CRP]s still correlated positively (P = 0.044), despite the fact that the surgery significantlly decresed the [BDNF]s and increased [CRP]s. No significant effect of the surgery on the [BDNF]p was found. We have concluded that serum BDNF concentration in breast cancer patients positively correlates with serum CRP both before and at 24 h after the surgery. Moreover, breast cancer surgery decreases serum BDNF concentration at 24 h after operation and increases [CRP]s.

The importance of the training-induced decrease in basal cortisol concentration in the improvement in muscular performance in humans.

Acute exercise-induced changes in cortisol concentration (C) and training related adaptation within hypothalamic-pituitary-adrenal (HPA) axis has been widely examined, but their influence on muscle strength performance is at best uncertain. Twenty four young healthy men were randomly assigned to an endurance training group (ET, n=12) or to a non-exercising controls (CON, n=12). ET performed supervised endurance training on cycle ergometer for 20 weeks. Endurance training program improved exercise capacity (14 % increase in power output generated at peak oxygen uptake - VO(2peak)), muscle strength performance (increase in MVC - maximal voluntary contraction - by 9 % and in TTF 50 % MVC - time to fatigue at 50 % MVC - by 21 %) and led to a decrease in basal serum C concentration (P=0.006) and an increase in basal testosterone to cortisol (T/C) and free testosterone to cortisol (fT/C) ratios (P=0.01 and P=0.02, respectively). It was found that the decrease in C concentration (deltaC) was positively correlated to the increase in local muscular endurance (deltaTTF 50 % MVC). No significant hormonal changes were seen in CON group. It is concluded that greater decrease in cortisol concentration after the endurance training is accompanied by poorer improvement in skeletal muscle performance in previously untrained subjects.

Treatment of Patients with Distant Metastases from Phyllodes Tumor of the Breast.

BACKGROUND: Here, the treatment methods and results of patients with phyllodes tumor of the breast (PT) with distant metastases at a single institution are presented. METHODS: A retrospective analysis was performed on a group of 295 patients with PT treated from 1952 to 2010. RESULTS: Distant metastases developed in 37 (12.5 %) patients; 3/160 (1.9 %) patients had benign PT, 6/36 (16.7 %) were considered borderline, and 28/99 (28.3 %) had malignant PT. Most frequently, the metastases were located in the lungs; 28 (75.7 %), bone 7 (18.9 %), brain 4 (10.8 %), and liver 2 (5.4 %). Metastases occurred on overage 21 months (2-57) after surgery. Patients with lung metastases were generally treated with monochemotherapy or polychemotherapy. In one patient Testosterone and in two patients resection of metastases combined with Doxorubicin were used. Patients with bones or brain metastases were treated with palliative radiotherapy only or combined with Doxorubicin. The mean survival (MS) from diagnosis of distant metastases (DM) was 7 months (2-17). The longest mean survival in patients with bones metastases was 11.8 months, the worst survival was for patients with brain metastases--2.8 months. Hormone therapy appeared to have low efficacy (MS: 2 months) as well as monochemotherapy (MS: 3-5 months). Improved MS was obtained using Doxorubicin (7 months) and Doxorubicin with Cisplatin, Cyclophosphamide, or Ifosfamide (9 months). CONCLUSION: The prognosis of patients with DM from PT is poor. The role of surgery and irradiation of such patients is very limited. There appears to be no role for the use of hormone therapy. This study showed that polychemotherapy with Doxorubicin and Ifosfamide suggest that it might be more effective than once thought.

Effects of delayed auditory and visual feedback on sequence production.

This study represents the first systematic comparison of the relative contributions of auditory and visual feedback to sequence production. Participants learned an isochronous melody that they performed on a keyboard and attempted to perform this sequence at a prescribed rate while auditory and visual feedback were manipulated. Delayed auditory feedback (DAF) and delayed visual feedback (DVF) both tended to slow production of the sequence. These effects were additive. There was no modulation of this effect of delay in either modality by the absence of feedback in the other. In contrast with past research, DAF did not increase timing variability, though DVF did. Motion analyses ruled out differences in salience of visual feedback between delayed and non-delayed conditions as an explanation of the effects of DVF. The results suggest that the effects of delayed feedback may be attributable to both sensorimotor interference and to conflicting information across feedback channels.

The dynamics of disruption from altered auditory feedback: Further evidence for a dissociation of sequencing and timing.

Three experiments were designed to test whether perception and action are coordinated in a way that distinguishes sequencing from timing (Pfordresher, 2003). Each experiment incorporated a trial design in which altered auditory feedback (AAF) was presented for varying lengths of time and then withdrawn. Experiments 1 and 2 included AAF that resulted in action-effect asynchronies (delayed auditory feedback) during simple tapping (Experiment 1) and melody production (Experiment 2). Asynchronous AAF immediately slowed production; this effect then diminished rapidly after removal of AAF. By contrast, sequential alterations of feedback pitch during melody production (Experiment 3) had an effect that varied over successive presentations of AAF (by increasing error rates) that lasted after its withdrawal. The presence of auditory feedback after withdrawal of asynchronous AAF (Experiments 1 and 2) led to overcompensation of timing, whereas the presence of auditory feedback did not influence performance after withdrawal of AAF in Experiment 3. Based on these results, we suggest that asynchronous AAF perturbs the phase of an internal timekeeper, whereas alterations to feedback pitch over time degrade the internal representation of sequence structure.

Endurance training of moderate intensity increases testosterone concentration in young, healthy men.

The aim of this study was to investigate the effect of short-term, moderate intensity and low volume endurance training on gonadal hormone profile in untrained men. Fifteen young, healthy men performed an endurance training of 5-week duration on a cycle ergometer. Before and after the exercise program all participants completed a maximal incremental test. Concentration of testosterone (T), sex hormone-binding globulin (SHBG) and cortisol (C) as well as blood morphology were determined in venous blood samples at rest both before and after the training. The training program resulted in 3.7% improvement of maximal oxygen uptake (VO(2max)) and 8.2% improvement of power output reached at VO(2max) (PO (max)). This was accompanied by significant increase in T (from 18.84+/-5.73 nmol.l(-1) to 22.03+/-6.61 nmol.l(-1), p = 0.0004) and calculated fT concentration (from 374+/-116 pmol.l(-1) to 470+/-153 pmol.l(-1), p = 0.00005). Moreover, the training caused a significant decrease in SHBG concentration (from 34.45+/-11.26 nmol.l(-1) to 31.95+/-10.40 nmol.l(-1), p = 0.01), whereas no significant changes were found in the cortisol concentration (334+/-138 nmol.l(-1) vs. 367+/-135 nmol.l(-1) for pre- and post-training measures, respectively, p = 0.50) and T/C and fT/C ratios. We have concluded that short-term, moderate intensity and low volume endurance training can significantly increase testosterone concentration in previously untrained men.

Regulation of acetyl-CoA carboxylase.

Acetyl-CoA carboxylase (ACC) catalyses the formation of malonyl-CoA, an essential substrate for fatty acid synthesis in lipogenic tissues and a key regulatory molecule in muscle, brain and other tissues. ACC contributes importantly to the overall control of energy metabolism and has provided an important model to explore mechanisms of enzyme control and hormone action. Mammalian ACCs are multifunctional dimeric proteins (530-560 kDa) with the potential to further polymerize and engage in multiprotein complexes. The enzymatic properties of ACC are complex, especially considering the two active sites, essential catalytic biotin, the three-substrate reaction and effects of allosteric ligands. The expression of the two major isoforms and splice variants of mammalian ACC is tissue-specific and responsive to hormones and nutritional status. Key regulatory elements and cognate transcription factors are still being defined. ACC specific activity is also rapidly modulated, being increased in response to insulin and decreased following exposure of cells to catabolic hormones or environmental stress. The acute control of ACC activity is the product of integrated changes in substrate supply, allosteric ligands, the phosphorylation of multiple serine residues and interactions with other proteins. This review traces the path and implications of studies initiated with Dick Denton in Bristol in the late 1970s, through to current proteomic and other approaches that have been consistently challenging and immensely rewarding.

CA125 in ovarian cancer: European Group on Tumor Markers guidelines for clinical use.

CA125 is currently the most widely used tumor marker for ovarian epithelial cancer. The aim of this article is to provide guidelines for the routine clinical use of CA125 in patients with ovarian cancer. Due to lack of sensitivity for stage I disease and lack of specificity, CA125 is of little value in the detection of early ovarian cancer. At present, therefore, CA125, either alone or in combination with other modalities, cannot be recommended for screening for ovarian cancer in asymptomatic women outside the context of a randomized controlled trial. Preoperative levels in postmenopausal women, however, may aid the differentiation of benign and malignant pelvic masses. Serial levels during chemotherapy for ovarian cancer are useful for assessing response to treatment. Although serial monitoring following initial chemotherapy can lead to the early detection of recurrent disease, the clinical value of this lead-time is unclear. CA125 is the ovarian cancer marker against which new markers for this malignancy should be judged.

Predictive value of SCC-Ag, CYFRA 21-1 and selected acute phase proteins in radiotherapy of pharyngeal and laryngeal cancer. A preliminary report.

The diagnostic sensitivity and specificity of tumor markers in head and neck cancers is not satisfactory. It is a stimulus for search of other biochemical indicators, among others determinations of acute phase proteins, helpful in head and neck cancers diagnostics and prognosis. In a group of 33 patients with squamous cell carcinoma of the pharynx and larynx (T1-4 N0-3 M0) CYFRA 21-1, SCC-Ag and acute phase proteins such as prealbumin, albumin, alpha-1 acid glycoprotein, alpha-1 antytrypsin, transferrin, ceruloplasmin and C-reactive protein (CRP) determinations were performed before radiotherapy. Significantly greater area under ROC curve for CYFRA 21-1 than for SCC-Ag was found. In T3-4 group, significantly lower albumin and higher AAG and CRP concentrations in comparison with T1-2 patients were observed. Multivariate analysis revealed that apart from tumor stage, elevated concentrations of SCC-Ag and/or CRP are independent unfavorable prognostic factors.

Vascular endothelial growth factor (VEGF) concentration in sera and tumor effusions from patients with ovarian carcinoma.

VEGF is an important angiogenic cytokine with a critical role in tumor angiogenesis. VEGF concentrations were measured using an ELISA assay, detecting VEGF165 isoform, in tumor cyst and/or ascitic fluids and in sera of 86 patients with malignant neoplasms and in 53 patients with benign ovarian neoplasms. VEGF levels were significantly elevated in the sera and cyst fluids of carcinoma patients compared with patients who had benign neoplasms. In carcinoma patients, statistically higher VEGF levels were detected in tumor effusions than in corresponding sera. The differences between VEGF values in sera and tumor effusions in relation to histological subtypes of ovarian carcinoma and FIGO stages were statistically insignificant. High VEGF levels in ascitic fluids appeared to be significantly associated with shorter disease-free survival and overall survival In multivariate analysis, besides FIGO stage and age of patients, only serum VEGF concentration was an independent prognostic factor for overall survival. The elevated VEGF levels in sera and tumor effusions of patients with FIGO stages I/II indicated that angiogenesis promoted by VEGF is a continuous process, independent of clinical advancement of the disease.

Glycolysis and pyruvate oxidation in cardiac hypertrophy--why so unbalanced?

Cardiac hypertrophy, induced by chronic pressure or volume overload, is associated with abnormalities in energy metabolism as well as characteristic increases in muscle mass and alterations in the structure of the heart. Hypertrophied hearts display increased rates of glycolysis and overall glucose utilization, but rates of pyruvate oxidation do not rise in step with rates of pyruvate generation. Glycolysis and glucose oxidation, therefore, become markedly less 'coupled' in hypertrophied hearts than in non-hypertrophied hearts. Because the pyruvate dehydrogenase complex (PDC) contributes so powerfully to the control of glucose oxidation, we set out to test the hypothesis that the function of PDC is impaired in cardiac hypertrophy. In this review we describe evidence indicating that the alterations in glucose metabolism in hypertrophied hearts cannot be explained simply by changes in PDC expression or control. Additional mechanisms that may lead to an altered balance of pyruvate metabolism in cardiac hypertrophy are discussed, with commentaries on possible changes in pyruvate transport, NADH shuttles, lactate dehydrogenase, and amino acid metabolism.

[Results of a randomized prospective trial comparing postoperative abdominopelvic radiotherapy with postoperative chemotherapy in early ovarian cancer]. / Résultats d'un essai prospectif randomisé comparant une radiothérapie abdominopelvienne postopératoire et une chimiothérapie postopératoire dans les cancers de l'ovaire précoces.

PURPOSE: In a prospective randomized trial, our aim was to evaluate and compare the tolerance and efficacy of postoperative radiotherapy and chemotherapy in the treatment of early ovarian cancer. MATERIAL AND METHODS: Between 1990 and 1996, 150 patients with ovarian cancer stage IA, IB grades G2-3, and all patients classified IC and IIA, who did not have evidence of residual disease after surgery, were randomized to two treatment branches: radiotherapy or chemotherapy (CH). In the radiotherapy branch (76 patients), a whole abdomen irradiation of 30 Gy in 24 fractions over 5 weeks, with a pelvic boost to 50 Gy, was delivered. In the chemotherapy branch (74 patients), there were six series of polychemotherapy separated with 3-weeks interval. In each series patients received association of cisplatin (50 mg/m2, d1), adriamycin (50 mg/m2, d1) and cyclophosphamide (500 mg/m2, d1). RESULTS: The tolerance of the treatment was good and comparable in both groups. In the radiotherapy branch, three late grade G3 intestinal complications were observed (three bowel obstructions, which required surgery in two cases). The actuarial survival rate without evidence of disease was 81% at 5 years for both groups. In our series we found that histological grade had the strongest influence on survival prognosis; it was the only significant factor in a multivariate analysis. Patients with grade G3 tumors had the worst survival. CONCLUSION: These data suggest that efficacy of postoperative radiotherapy and chemotherapy administered to our patients with early ovarian cancer gave approximately identical results.

CYFRA 21-1, TPA-M, TPS, SCC-Ag and CEA in patients with squamous cell lung cancer and in chemical industry workers as a reference group.

In etiology of lung cancer chemical carcinogenesis seems to be a very important factor. In the studies presented here the diagnostic usefulness of tumor markers in lung cancer was evaluated, using as a reference group workers of a chemical plant producing chromite and chromate pigments. The investigations of CYFRA 21-1, TPA-M, TPS, CEA and SCC-Ag were performed before treatment in a group of 76 squamous cell lung cancer patients in different stages of disease and in a reference group of 75 workers of the chemical company, who had been exposed to hexavalent chromium for longer than 1 year and had no clinical or radiological symptoms of lung diseases. In the squamous cell lung cancer group concentrations of all analyzed tumor markers were considered to be significantly higher than in the reference group. TPA assay demonstrated higher diagnostic performance than CYFRA 21-1 and the remaining tumor markers. At 0.95 specificity, the sensitivity of TPA was 0.79, CYFRA 21-1 -0.76, of TPS -0.29 whilst of CEA and SCC-Ag -0.31. The univariate analysis showed a significant prognostic value for clinical stages, only for CYFRA 21-1 and SCC-Ag. A significant relationship between marker level and survival was observed for CYFRA 21-1 as well as SCC-Ag levels. In a multivariate analysis CYFRA 21-1 and/or TPS remained significant predictors of survival.

Bimodal activation of acetyl-CoA carboxylase by glutamate.

Acetyl-CoA carboxylase (ACC) catalyzes the formation of malonyl-CoA, an essential substrate for fatty acid biosynthesis and a potent inhibitor of fatty acid oxidation. Here, we provide evidence that glutamate may be a physiologically relevant activator of ACC. Glutamate induced the activation of both major isoforms of ACC, prepared from rat liver, heart, or white adipose tissue. In agreement with previous studies, a type 2A protein phosphatase contributed to the effects of glutamate on ACC. However, the protein phosphatase inhibitor microcystin LR did not abolish the effects of glutamate on ACC activity. Moreover, glutamate directly activated purified preparations of ACC when protein phosphatase activity was excluded. Phosphatase-independent ACC activation by glutamate was also reflected by polymerization of the enzyme as judged by size-exclusion chromatography. The sensitivity of ACC to direct activation by glutamate was diminished by treatment in vitro with AMP-activated protein kinase or cAMP-dependent protein kinase or by beta-adrenergic stimulation of intact adipose tissue. We conclude that glutamate, an abundant intracellular amino acid, induces ACC activation through complementary actions as a phosphatase activator and as a direct allosteric ligand for dephosphorylated ACC. This study supports the general hypothesis that amino acids fulfill important roles as signal molecules as well as intermediates in carbon and nitrogen metabolism.

Leukemoid reaction in extremely low-birth-weight infants.

The objective of this paper was to determine the incidence of leukemoid reaction and to evaluate its relationship with maternal and neonatal factors in extremely low-birth-weight (ELBW) infants. The design a case-controlled retrospective study of all live-born ELBW infants (<1000 g) over a period of 2 years, from July 1994 to June 1996. A total of 60 preterm infants were born during the study period, and are included in this report. The infants who demonstrated leukemoid reaction formed the study group, while the remainder formed the control group. Leukemoid reaction was defined as a white blood cell (WBC) count > or = 50,000/mm3. The relationship between maternal and neonatal variables and WBC counts was studied. Nine of the 60 infants studied demonstrated counts >50,000/mm3, with an incidence of 15%. There was no significant association demonstrated between maternal or neonatal variables and leukemoid reaction. Patients with leukemoid reaction had a better overall survival. Leukemoid reaction in ELBW infants is a rare and recently documented phenomenon. In our study the incidence was 15%. Although many factors have been postulated as a cause of this phenomenon, we could not demonstrate any relationship between these factors and high WBC counts, including sepsis and the use of antenatal steroids, the two most likely variables. It was interesting to note that the infants who were able to mount a leukemoid response had a better chance of survival than those who did not.

[Radiotherapy for stage III, inoperable, asymptomatic small cell lung cancer. Final results of a prospective randomized study (240 patients)]. / Radiothérapie du cancer bronchique non à petites cellules de stade III, inopérable, asymptomatique. Résultats définitifs d'un essai prospectif randomisé (240 patients).

PURPOSE: To report the results of a prospective randomized study concerning the role of radiotherapy in the treatment of stage III, unresectable, asymptomatic non-small cell lung cancer. MATERIAL AND METHODS: Between 1992 and 1996, 240 patients with stage III, unresectable, asymptomatic non-small cell lung cancer were enrolled in this study, and sequentially randomized to one of the three treatment arms: conventional irradiation, hypofractionated irradiation and control group. In the conventional irradiation arm (79 patients), a dose of 50 Gy in 25 fractions in five weeks was delivered to the primary tumor and the mediastinum. In the hypofractionated irradiation arm (81 patients), there were two courses of irradiation separated by an interval of four weeks. In each series, patients received 20 Gy in five fractions in five days, in the same treatment volume as the conventional irradiation group. In the control group arm, 80 patients initially did not receive radiotherapy and were only observed. Delayed palliative hypofractionated irradiation (20-25 Gy in four to five fractions in four to five days) was given to the primary tumor when major symptoms developed. RESULTS: The two-year actuarial survival rates for patients in the conventional irradiation, hypofractionated irradiation and control group arms were 18%, 6% and 0%, with a median survival time of 12 months, nine months and six months respectively. The differences between survival rates were statistically significant at the 0.05 level. CONCLUSION: Although irradiation provides good palliation, the results are disappointing. The comparison of conventional and hypofractionated irradiation shows an advantage for conventional schedules.

[Gas exchange, blood acid-base balance and mechanical muscle efficiency during incremental levels of exertion in young healthy individuals]. / Wymiana gazowa, równowaga kwasowo-zasadowa krwi i sprawnosc mechaniczna miesni w wysilku o stopniowo wzrastajacej mocy u mlodych zdrowych ludzi.

UNLABELLED: In this study we have evaluated the changes in gas exchange variables, blood acid-base balance and the mechanical efficiency of muscle in healthy young men during an incremental exercise test. Twenty-six healthy men: age 22.1 +/- 1.4 (mean +/- SD) years, body mass 73.6 +/- 7.4 kg, height 179 +/- 8 cm, were subjects in this study. The subjects performed an incremental exercise test on a cycloergometer at a pedalling rate of 70 rev.min-1. The exercise test started at a power output of 30 W, followed by an increase of power output by 30 W every 3 minutes. Gas exchange variables were measured continuously (breath by breath). Antecubital blood samples for acid-base balance variables and plasma lactate concentration [La]pl were taken at the end of each 3-minute step. The lactate threshold (LT) in this study was defined as the highest power output above which [La]pl showed a sustained increase of > 0.5 mmol.l-1.step-1. The power output at LT amounted to 127 +/- 28 W. It corresponded to 45% of the maximal power output (MPO) reached at maximal oxygen uptake (VO2 max). The oxygen uptake at the LT amounted to 1734 +/- 282 ml.min-1 and corresponded to 48% of VO2 max (3726 +/- 363 ml.min-1). The minute ventilation at the LT amounted to 47.8 +/- 7.5 l, and its increase to the level of 125.7 +/- 19.7 l reached at the MPO was obtained mainly by intensification of breathing frequency from 23.8 +/- 3.31.min-1 to 43 +/- 5.91.min-1, for LT and MPO respectively. Analysis of the changes in PETCO2 during the incremental exercise test showed significant differences between subjects. One could recognise a group of subjects (n = 8) with high values of PETCO2 (above 45 mmHg) and a group of subjects (n = 8) with lower values of PETCO2 (below 43 mmHg). However, no significant differences in exercise tolerance, expressed by the level of MPO and maximal oxygen uptake, were found between those groups of subjects. The mechanical efficiency calculated on the basis of power output/net oxygen uptake ratio during cycling at a power output of 60 W amounted to 24.1 +/- 3.8 percent, at the LT 25.8 +/- 2.1%, whereas at the maximal power output a significant (p < 0.01) drop in muscle efficiency occurred, to the value of 23.1 +/- 1.6%. This drop in muscle efficiency occurring at the MPO may be an important factor limiting exercise tolerance when performing high power output exercise. IN CONCLUSION: The above presented data illustrate the physiological responses to incremental exercise and the level of exercise tolerance, which may serve as a reference point for the population of healthy, young physically active Polish students.

Pharyngeal acid reflux events in patients with vocal cord nodules.

OBJECTIVE: Gastroesophageal reflux has been implicated in the pathogenesis of vocal cord nodules. However, a cause-and-effect relationship has not been established. Because documentation of pharyngeal acid reflux events makes this correlation more plausible, the aim of the present study was to determine the frequency of pharyngeal acid reflux events in patients with vocal cord nodules. METHODS: Eleven patients with vocal cord nodules (mean age, 42 +/- 6 years) and eleven healthy volunteers (mean age, 45 +/- 6 years) were studied. Patients underwent barium esophagram and ambulatory 24-hour simultaneous three-site pharyngoesophageal pH monitoring. Controls only had ambulatory 24-hour simultaneous three-site pH monitoring. In the ambulatory pH monitoring studies, pH was recorded from the manometrically determined sites of pharynx (2 cm above upper esophageal sphincter), proximal esophagus (10 cm distal to pharyngeal site), and distal esophagus (5 cm above the lower esophageal sphincter). Pharyngeal acid reflux event was deemed acceptable if all three sites recorded a decrease in pH below 4 which was not related to meal or drinking. RESULTS: Pharyngeal acid reflux events occurred in seven of 11 patients with vocal cord nodules (1-4 episodes) and two of 11 controls (1-2 episodes) (P < .05). In both groups all pharyngeal acid reflux events occurred in upright position and were not associated with belching or coughing. Barium studies documented hiatal hernia in two patients and gastroesophageal reflux in five of 11 patients. However, none of the esophageal reflux events reached the pharynx on barium esophagram. CONCLUSIONS: Prevalence of pharyngeal acid reflux events is significantly higher in patients with vocal cord nodules compared with normal controls and suggests a contributory role for gastroesophagopharyngeal acid reflux in the pathogenesis of some vocal cord nodules.

Mutations of the FLP recombinase gene that cause a deficiency in DNA bending and strand cleavage.

We have used site-directed mutagenesis to change several amino acids of the C-terminal portion of the FLP recombinase of Saccharomyces cerevisiae. These residues are absolutely conserved among the six FLP-like proteins from various yeast strains. We have examined the ability of the altered proteins to catalyze recombination in vivo and in vitro and to perform various partial steps of the reaction in vitro. Two of the mutations produced a partial defect in DNA binding but the remainder resulted in normal binding. All of these mutations caused impairment of the ability of the protein to induce the type II bend of the FRT site, and some of these proteins were also defective in DNA strand cleavage. None of the mutations affected the ability of the proteins to perform synapsis between two FRT sites, but some were defective in strand ligation. Interestingly, some mutant proteins showed impairment of the initial stages of the recombination reaction on a linear substrate and yet they maintained the ability to resolve a Holliday intermediate in the reaction. We conclude that this conserved region of the FLP protein is important for the early stage(s) of the recombination reaction.

[Value of plasma testosterone, carcinoembryonic antigen and CA 19-9 in the differential diagnosis of pancreatic carcinoma and chronic pancreatitis]. / Przydatnosc oznaczania stezenia testosteronu, antygenu karcinoembrionalnego oraz CA 19-9 w surowicy w diagnostyce róznicowej raka i przewleklego zapalenia trzustki.

Diagnostic value was assessed of serum testosterone concentration and compared with that of serum assay of CEA and CA 19-9 in the differential diagnosis of pancreatic cancer (PC) and chronic pancreatitis (CP). Thirty-six patients with PC were compared with thirty-two CP patients. The sensitivity of CA 19-9 (76.9%) in detecting PC was greater than that of testosterone and CEA (30.6% and 30.8%, respectively). The specificity of testosterone and CA 19-9 were comparable (93.7% and 96.4%, respectively). The combination of tests did not enhance the sensitivity and specificity of each test when used alone. The serum CA 19-9 concentration in PC patients was significantly higher then in patients with colon cancer, gastric cancer and benign gastrointestinal diseases.