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1.
Béla Nagy Zsolt Bene Zsolt Fejes Sonya L. Heltshe David Reid Nicola J. Ronan Yvonne McCarthy Daniel Smith Attila Nagy Elizabeth Joseloff György Balla János Kappelmayer Milan Macek Scott C. Bell Barry J. Plant Margarida D. Amaral István Balogh 《Journal of cystic fibrosis》2019,18(2):271-277
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.Methods
In this retrospective clinical study, 3 independent CF patient cohorts (US-American: 29, Australian: 12 and Irish: 19 cases) were enrolled carrying at least one Class III CFTR CF-causing mutation (p.Gly551Asp) and being treated with CFTR potentiator ivacaftor. Plasma HE4 was measured by immunoassay before treatment (baseline) and 1–6?months after commencement of ivacaftor, and were correlated with FEV1 (% predicted), sweat chloride, C-reactive protein (CRP) and body mass index (BMI).Results
After 1?month of therapy, HE4 levels were significantly lower than at baseline and remained decreased up to 6?months. A significant inverse correlation between absolute and delta values of HE4 and FEV1 (r?=??0.5376; P?<?.001 and r?=??0.3285; P?<?.001), was retrospectively observed in pooled groups, including an independent association of HE4 with FEV1 by multiple regression analysis (β?=??0.57, P?=?.019). Substantial area under the receiver operating characteristic curve (ROC-AUC) value was determined for HE4 when 7% mean change of FEV1 (0.722 [95% CI 0.581–0.863]; P?=?.029) were used as classifier, especially in the first 2?months of treatment (0.806 [95% CI 0.665–0.947]; P?<?.001).Conclusions
This study shows that plasma HE4 levels inversely correlate with lung function improvement in CF patients receiving ivacaftor. Overall, this potential biomarker may be of value for routine clinical and laboratory follow-up of CFTR modulating therapy. 相似文献2.
The differences between the postprandial mixing or propulsion and the interdigestive motility of the gastrointestinal (GI)
tract are already known. Earlier studies showed dose-dependent differences in the effects of erythromycin on interdigestive
motility. The various GI side-effects (vomiting, diarrhoea) also suggest that there are different effects of erythromycin
on the GI motility. The aim of our study was to examine postprandially the propulsive effects of different doses of erythromycin
on the movement of intraluminal contents in the upper GI tract of the rat. The animals were fasted for 24 h before the experiments
but water was given freely. The rats received 1.5 ml 1.5% methylcellulose painted with 0.05% phenol-red intragastrically (test
solution). Erythromycin(E. lactobionate) was given intravenously at doses of 0.05, 0.1, 0.25, 0.5, 1.0 and 5.0 mg/kg 15 min before the administration of a test solution.
The animals were sacrificed 20,60 and 120 min after administration of methylcellulose, when the distance between the front
of the painted intraluminal contents and the pylorus was measured and expressed as a percentage of the total length of small
intestine. The phenol-red content in the stomach and small intestine was measured spectrophotometrically and the gastric emptying
was calculated from the ratio of the measured total and intestinal phenol-red content. Our results showed that the small doses
of erythromycin (0.1 and 0.25 mg/kg) accelerated gastric emptying after 20 min but did not change significantly the propulsive
motility of upper small intestine; however, large doses of erythromycin (1.0 and 5.0 mg/kg) decreased gastric emptying and
upper GI motility after 20 and 60 min. In summary, the prokinetic action of small doses of erythromycin was demonstrated,
but its effecttime on GI motility is short and the ratio of the stimulating and inhibitory doses is 1:10.
This paper was presented at the Section of IUPHAR GI Pharmacology Symposium on ’Biochemical pharmacology as an approach to
gastrointestinal disorders (basic science to clinical perspectives)‘, October 12-14, 1995, Pécs, Hungary. 相似文献
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Levente Gáspár Zoltán Jónás László Kiss György Vereb Zoltán Csernátony 《European journal of orthopaedic surgery & traumatology : orthopedie traumatologie》2009,19(6):403-407
Background Coccygodynia can cause severe pain and disability in patients. There are contradictions in the literature regarding the final
results of coccygectomy for coccygodynia. We evaluated the long-term effects of coccygectomy on the intensity, characteristics,
and manifestation of pain caused by coccygodynia to determine the adequacy of operation among treatment modalities.
Materials and methods Thirty-four patients with coccygodynia were treated by coccygectomy. In 22 cases, trauma, and in one case childbirth was the
cause. 11 cases were regarded as idiopathic. The intensity, characteristics of pain, and the most painful activities were
evaluated at an average of 7.6 (3–18) years of follow-up time.
Results Before the operation, all 34 patients had pain while sitting, moreover, 26 of them had pain during standing, walking, at night
or a combination of these. 21 patients had intolerable or very intensive, mainly acute, sharp or burning pain. 11 patients
had dyschesia, 2 had dysuria and 6 had dyspareunia. At follow-up, 7 patients were completely free of pain, 15 others had moderate,
11 medium, and only one patient had severe, but none had intolerable pain. Only seven patients had acute, sharp or burning
pain postoperatively. The decrease of average pain score from 8.0 to 3.2 was significant (P < 10−12). The number of the patients with dyschesia and dyspareunia decreased from 11 to 7 and from 6 to 3, respectively. Two patients
had dysuria, but their complaints did not change after the operation. One of the two patients who needed reoperation had an
excellent final result, while the other remained unchanged. 12 and 16 patients (together 82%) regarded the final result of
the operation excellent and good, respectively. The condition of five others did not change, while one became worse. The patients
with younger age, smaller body mass index, and less co-morbidities had better final result. There were no serious complications.
Conclusion Coccygectomy for coccygodynia is a safe method to decrease the intensity of pain and other complaints of the patients. The
operation can be the choice of treatment if conservative measures fail. 相似文献
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Ohne Zusammenfassung 相似文献
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Bronwyn A. Kingwell Lisa Krause Stevo Julius 《Clinical and experimental pharmacology & physiology》1994,21(1):31-39
1. Left ventricular (LV) hypertrophy has been implicated in the reduction of baroreflex sensitivity present in hypertension. The aim of the current study was to investigate the mean arterial pressure-heart rate reflex (MAP-HR) in a model which induced left ventricular hypertrophy but no sustained blood pressure elevation. 2. Five mongrel dogs were exposed to transient blood pressure elevation of between 20 and 30 mmHg, through hindlimb compression using a pneumatic pressure suit, for 7 h per day, 6 days per week for 6 weeks. Resting blood pressure was not altered by the 6 week hindlimb compression intervention. 3. Echocardiographically determined LV mass (mean ± s.e.m.) was 116.0 ± 7.4 g prior to hindlimb compression (baseline) and elevated to 125.4 ± 8.1 g (P= 0.003) after 6 weeks of compression. A reduction in the early (E) to late (A) transmitral diastolic flow ratio (E/A) from 1.80 ± 0.06 at baseline to 1.54 ± 0.09 (P = 0.037) after the 6 week intervention suggested that cardiac compliance was reduced. 4. The maximum gain of the MAP-HR reflex, studied using the ‘steady-state’ drug technique, when blood pressure was normal, showed a trend for reduction from 3.85 ± 0.43 beats/min per mmHg at baseline to 3.10 ± 0.45 beats/min per mmHg (P= 0.067) after 6 weeks of compression. This gain reduction became significant after β-adrenoceptor blockade with propranolol (3.13 ± 0.55 vs 2.32 ± 0.25 beats/min per mmHg; P= 0.039). Covariant analysis showed a significant inverse correlation between LV mass and maximum gain (r= 0.96; P<0.001) during the 6 week compression period. 5. The MAP-HR reflex changes in this model mimic those present in hypertension and implicate cardiac hypertrophy as one possible mediator. 相似文献
9.
Gy?rgy Lang Attila Cseke? Georgios Stamatis Ludwig Lampl Leif Hagman Gabriel Mihai Marta Michael Rolf Mueller Walter Klepetko 《European journal of cardio-thoracic surgery》2004,25(2):160-166
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. 相似文献
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