Human epididymis protein 4 (HE4) levels inversely correlate with lung function improvement (delta FEV1) in cystic fibrosis patients receiving ivacaftor treatment

Background

We have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy.

Characterizing luminous efficiency functions for a simulated mesopic night driving task based on reaction time

The objective of this study is to test the luminous efficiency functions V(lambda), V'(lambda), V(10)(lambda) and their linear combinations on the basis of a data set gained from a simulated mesopic night-time driving experiment. Another aim is to provide 'real-world' data for the 'X framework' or 'linear combination model', and to find out its limits in a practical situation. Human performance was measured by the reaction time method. Results show that the single parameter of the linear combination of photopic and scotopic luminous efficiency functions can be determined analytically with little variation for a given mesopic background luminance level and a given visual target colour, but the computation leads to considerable deviations comparing all three target colours (red, green and blue) used in the experiment. The conclusion for the given experimental conditions is that the single parameter of the linear combination model has an increasing deviation for lower background luminance levels.     

Simultane Radiochemotherapie mit intraluminaler HDR-Brachytherapie des Ösophaguskarzinoms

PURPOSE: To study efficacy and toxicity of radiochemotherapy in esophageal cancer including initial endoluminal high-dose-rate brachytherapy (HDR-BT). PATIENTS AND METHODS: Between 01/1995 and 06/2005, 61 patients with esophageal cancer were treated preoperatively with definitive and palliative intent. Treatment started with intraluminal HDR-BT for recanalization of the esophagus (single fraction size of 8 Gy in 0.5 cm depth, three times, q7d) followed by external-beam radiation therapy (50 Gy total dose, 5 x 2 Gy/week, 25 fractions in 5 weeks). Chemotherapy was started simultaneously with external irradiation (three courses of cisplatin and 5-fluorouracil, q21d). RESULTS: Swallowing function improved in 55/61 patients (dysphagia classification according to the RTOG), and worsened in 6/61 patients, respectively. Median duration of symptomatic improvement was 11 months, median follow-up 12 months (range 3-68 months). Following simultaneous radiochemotherapy, tumor resectability was achieved in 7/25 patients of the neoadjuvant group, and the histological specimen showed complete remission in 6/7 patients. CONCLUSION: These results indicate a favorable effect of simultaneous radiochemotherapy starting with endoluminal HDR-afterloading-( AL-)BT in esophageal cancer.     

Effects of monoamine uptake inhibitors given early postnatally on monoamines in the brain stem,caudate/putamen and cortex,and on dopamine D1 and D2 receptors in the caudate/putamen

Summary Rats were treated with desipramine 5mg/kg, nomifensine 10mg/kg, zimelidine 25 mg/kg or with 0.9% sodium chloride once a day during the second and third weeks after birth, and brain stem, caudate/putamen and cortical monoamines, and caudate/putamen dopamine D₁ (³[H]SCH 23390) and D₂ (³[H]spiroperidol) receptor binding were measured when rats were at two months of age. In the brain stem, the concentration of 3-methoxy-4-hydroxy-phenyl glycol was increased in nomifensine rats and the ratio of 5-hydroxyindoleacetic acid to 5-hydroxytryptamine was increased in zimelidine rats. In the caudate/putamen, the concentrations of 3,4-dihydroxyphenylacetic acid and homovanillic acid and the ratio of homovanillic acid to dopamine were increased in desipramine rats; neither³[H]SCH 23390 nor³[H]spiroperidol binding were affected by any of the three monoamine uptake inhibiting antidepressants studied. In the cortex, the ratio of 5-hydroxyindoleacetic acid to 5-hydroxytryptamine was increased in desipramine and zimelidine rats. The findings suggest that desipramine but not nomifensine increases the metabolism of dopamine in the caudate/ putamen and nomifensine but not desipramine increases the metabolism of norepinephrine in the brain stem, and furthermore that the metabolism of serotonin is affected by desipramine as well as by zimelidine. It is possible that also treatment of women with these drugs during late pregnancy causes long-lasting changes in the brain of human fetus.     

Efficacy and safety of topical application of human fibrinogen/thrombin-coated collagen patch (TachoComb) for treatment of air leakage after standard lobectomy.

OBJECTIVES: Persisting air leakage after pulmonary resection remains a significant problem. The aim of the study was to evaluate the incidence of air leakage after standard lobectomy and test the efficacy and safety of TachoComb (TC). METHODS: A total of 189 patients undergoing lobectomy were enrolled in a multi-centre, open, randomised, and prospective study to test the efficacy and safety of TachoComb (TC) for air leakage treatment. Air leakage was assessed by water submersion test, and scored as grades 0 if no, 1 if countable, 2 if a stream of and 3 if coalescent bubbles have been observed. Any sites with grade 3 air leakage received further stapling or limited suturing until grade 0, 1 or 2 was obtained. Treatment of air leakage was done with TC or suturing according to randomisation. Air leakage was assessed by further submersion tests. Postoperative air leakage was assessed using the Pleur-Evac system. RESULTS: Overall incidence of air leakage 48+/-6 h after surgery was 34% for TC and 37% for standard treatment (P=0.76). The reduction of intra-operative air leak intensity in the subgroup with grades 1-2 was significantly higher for the TC group (P=0.015). Postoperative air leakage intensity in the subgroup with air leakage grades 1-2 was lower for TC than standard treatment (P=0.047). The mean duration of postoperative air leakage in the subgroup with grades 1-2 was shorter for the TC group than for standard treatment, i.e. 1.9+/-1.4 vs. 2.7+/-2.2 days (P=0.015). CONCLUSIONS: TC could be proven as well-tolerated and safe. In the subgroup of patients with established air leakage, TC showed superior potential in reduction of intra-operative air leakage as well as in reduction of intensity and duration of postoperative air leakage.     

Magnesium-orotate supplementation for idiopathic infertile male patients: a randomized, placebo-controlled clinical pilot study.

A randomized, placebo-controlled clinical pilot study was performed in order to examine the effect of magnesium-orotate in male idiopathic infertility. Ten males were treated daily for 90 consecutive days with 3000 mg magnesium-orotate (Magnerot) tablets (Group M). As a control, ten other males were treated in the same way with placebo (Group P). Conventional microscopic sperm characteristics (sperm concentration, motility ratio, total number of motile sperm cells, normal morphology ratio), plus total and ionized magnesium levels in seminal plasma and blood serum were evaluated both prior to treatment and on day 90, at the conclusion of the study. No significant changes in sperm characteristics, blood ionized or total Mg, or ejaculate total Mg levels were detected. However, ejaculate ionized Mg levels increased in Group M from 0.18 +/- 0.05 to 0.30 +/- 0.05 (mmol/l; mean +/- SD, p < 0.05). Within the observation period of 3 months, one pregnancy occurred in the partner of a male from Group M. In conclusion, magnesium-orotate treatment at a dose of 3000 mg/day leads neither to a significant improvement of sperm variables nor does it increase the pregnancy rates of female partners of treated males as compared to those of controls. Thus, magnesium-orotate treatment was not shown to be effective therapy for idiopathic male infertility.     

Mistyping of angiotensinogen M235T alleles.

Conflicting results are to be found in the literature on the relationship between the M235T polymorphism of the angiotensinogen (AGT) gene and hypertension. The controversy may be due to insufficient numbers of subjects, the variability of the inclusion criteria and the different genotype analysis methods used. We have experienced that the most frequently used, original polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method involves significant uncertainties when the TT genotype is determined, independently of the restriction digestion. To make the determination more accurate, we improved the PCR by designing a new antisense primer containing only one mismatch instead of the two in the original protocol and also by adding DMSO to the PCR reaction mixture. The original and our improved methods were compared by using DNA from 123 patients: parallel determinations resulted in values of 33 MM, 90 MT and 0 TT with the original method and of 33 MM, 56 MT and 34 TT with the improved RFLP protocol. In summary, a plausible explanation for some of the conflicting data published on AGT M235T polymorphism may be that inaccuracies arose during the determination of the genotype.     

Evidence that ATP released from the postsynaptic site by noradrenaline, is involved in mechanical responses of guinea-pig vas deferens: cascade transmission.

The release of endogenous ATP and [3H]noradrenaline, and the mechanical response of the guinea-pig vas deferens to field stimulation of its motor nerves were examined using a perfusion system. The release of ATP at rest was 0.83 +/- 0.13 pmol/g per min, and ATP released by field stimulation (8 Hz, 480 shocks) was 5.47 +/- 1.23 pmol/g. The evoked release was completely inhibited when Ca2+ was removed and 1 mM EGTA was added, or by 1 microM tetrodotoxin. The release of ATP and [3H]noradrenaline in response to field stimulation was constant with an S2/S1 ratio of 1.10 +/- 0.11 for ATP and 0.92 +/- 0.03 for [3H]noradrenaline, respectively (where S1 and S2 are stimulation periods). Prazosin (1 microM), a potent alpha 1-adrenoceptor antagonist, significantly reduced the stimulation-evoked release of ATP by 75% and significantly reduced both mechanical twitch and tonic responses, but enhanced the release of [3H]noradrenaline. This finding indicates that there is an alpha 1-adrenoceptor-mediated release of endogenous ATP. However, the prazosin-insensitive portion of ATP release (25%) is considered to be of presynaptic origin. The stimulation of alpha 1-adrenoceptors by 1-noradrenaline or methoxamine in concentrations ranging from 10 to 100 microM resulted in a concentration-dependent release of ATP and a biphasic contraction of the vas deferens: a twitch response was followed by a tonic contraction. Prazosin (1 microM) completely prevented the effect of 1-noradrenaline or methoxamine on both ATP release and mechanical response. When Ca2+ was omitted and EGTA (1 mM) was added, 1-noradrenaline was still able to release ATP but failed to produce contraction. Nifedipine, a Ca-channel and ATP receptor antagonist, reduced the twitch contraction and enhanced the release of ATP from muscle in response to noradrenaline administration. This finding indicates that the release of ATP from the muscle is not linked to mechanical contraction. When the vas deferens was made deficient in noradrenaline by 6-hydroxydopamine pretreatment (100 + 250 mg/kg, i.p.), electrical field stimulation failed to release [3H]noradrenaline and ATP. Under these conditions, exogenous 1-noradrenaline was much more effective in releasing ATP from the smooth muscle, and producing twitch responses, followed by a tonic contraction. After reserpine pretreatment (2 x 5 mg/kg, i.p.), the field stimulation-evoked release of ATP and both phases of contraction were markedly reduced.(ABSTRACT TRUNCATED AT 400 WORDS)