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Biomedical subjects

R Romagnoli

Publications and source records attributed to R Romagnoli.

At least 37 records · Page 2Linked to original sources
PubMed2001

Denervated stomach as an esophageal substitute recovers intraluminal acidity with time.

OBJECTIVE: To determine whether the denervated stomach as an esophageal substitute recovers normal intraluminal acidity with time. SUMMARY BACKGROUND DATA: Bilateral truncal vagotomy to the stomach as an esophageal substitute reduces both gastric acid production and antral motility, but a spontaneous motor recovery process takes place over years. METHODS: Intraluminal gastric pH and bile were monitored during a 24-hour period 1 to 195 months after transthoracic elevation of the stomach as esophageal replacement in 91 and 76 patients, respectively. Nine patients underwent a second gastric pH monitoring after a 3-year period. The percentages of time that the gastric pH was less than 2 and bile absorbance exceeded 0.25 were calculated in reference to values from 25 healthy volunteers. Eighty-nine upper gastrointestinal endoscopies were performed in 83 patients. Patients were divided into three groups depending on length of follow-up: group 1, less than 1 year; group 2, 1 to 3 years; group 3, more than 3 years. RESULTS: The prevalence of a normal gastric pH profile was 32.3% in group 1, 81.5% in group 2, and 97.6% in group 3. The percentage of time that the gastric pH was less than 2 increased from group 1 (27.3%) to group 2 (56.1%) and group 3 (70.5%), parallel to an increase in the prevalence of cervical heartburn and esophagitis. The percentage of time that the gastric pH was less than 2 increased from 28.7% to 81.2% in the nine patients investigated twice. Exposure of the gastric mucosa to bile was 12.8% in patients with a high gastric pH profile versus 19.3% in those with normal acidity. In the esophageal remnant in six patients, Barrett's metaplasia developed, intestinal (n = 2) or gastric (n = 4) in type. CONCLUSIONS: Early after vagotomy, intraluminal gastric acidity is reduced in two thirds of patients, but the stomach recovers a normal intraluminal pH profile with time, so that in more than one third of patients, disabling cervical heartburn and esophagitis develop. The potential for the development of Barrett's metaplasia in the esophageal remnant brings into question the use of the stomach as an esophageal substitute in benign and early neoplastic disease.

Adult↗
PubMed2001

Skeletonizing en bloc esophagectomy for cancer.

OBJECTIVE: To evaluate the long-term outcome of patients with esophageal cancer after resection of the extraesophageal component of the neoplastic process en bloc with the esophageal tube. SUMMARY BACKGROUND DATA: Opinions are conflicting about the addition of extended resection of locoregional lymph nodes and soft tissue to removal of the esophageal tube. METHODS: Esophagectomy performed en bloc with locoregional lymph nodes and resulting in a real skeletonization of the nonresectable anatomical structures adjacent to the esophagus was attempted in 324 patients. The esophagus was removed using a right thoracic (n = 208), transdiaphragmatic (n = 39), or left thoracic (n = 77) approach. Lymphadenectomy was performed in the upper abdomen and lower mediastinum in all patients. It was extended over the upper mediastinum when a right thoracic approach was used and up to the neck in 17 patients. Esophagectomy was carried out flush with the esophageal wall as soon as it became obvious that a macroscopically complete resection was not feasible. Neoplastic processes were classified according to completeness of the resection, depth of wall penetration, and lymph node involvement. RESULTS: Skeletonizing en bloc esophagectomy was feasible in 235 of the 324 patients (73%). The 5-year survival rate, including in-hospital deaths (5%), was 35% (324 patients); it was 64% in the 117 patients with an intramural neoplastic process versus 19% in the 207 patients having neoplastic tissue outside the esophageal wall or surgical margins (P <.0001). The latter 19% represented 12% of the whole series. The 5-year survival rate after skeletonizing en bloc esophagectomy was 49% (235 patients), 49% for squamous cell versus 47% for glandular carcinomas (P =.4599), 64% for patients with an intramural tumor versus 34% for those with extraesophageal neoplastic tissue (P <.0001), and 43% for patients with fewer than five metastatic nodes versus 11% for those with involvement of five or more lymph nodes (P =.0001). CONCLUSIONS: The strategy of attempting skeletonizing en bloc esophagectomy in all patients offers long-term survival to one third of the patients with resectable extraesophageal neoplastic tissues. These patients represent 12% of the patients with esophageal cancer suitable for esophagectomy and 19% of those having neoplastic tissue outside the esophageal wall or surgical margins.

Adenocarcinoma↗
PubMed2001

[Pulse inversion ultrasonography with ultrasonography contrast media (levovist) in the evaluation of hepatic metastasis].

PURPOSE: To evaluate if Pulse Inversion Harmonic Imaging with contrast agent injection (Levovist) is able to determine an increase of echogenicity in normal hepatic parenchyma, and to compare its capability to detect metastatic focal lesions with that of standard US and spiral CT. To define and standardize the technical and methodological aspects of this new technique. MATERIAL AND METHODS: A selected group of 72 patients (42 males and 30 females) with clinical and instrumental suspect of hepatic metastatic lesions was included in the prospective study. Each patient was examined by conventional ultrasound (US), Pulse Inversion Harmonic Imaging (PI) and spiral-CT (spCT). US examination was performed using an HDI 5000 (ATL, Bothell, USA) equipped with a broadband probe (5.0-2.0 MHz). 2.5 g Levovist (Schering AG-Berlin) was administered intravenously, at concentration of 300 mg/ml and a flow rate of 7 ml/min. Video clips obtained with the acquired images before and after contrast medium administration were transferred to a magnet optic disk unit. Examinations were evaluated by an experienced radiologist blindly on a workstation that allowed a qualitative-quantitative analysis. SpCT images were evaluated separately by another experienced radiologist. US images were evaluated qualitatively (number of lesions, site of lesion, diameter of the smallest lesion detectable) and quantitatively (increase in parenchymal echogenicity 20", 40", 60" and 5' after the injection of contrast agent). RESULTS: In all cases examined, the echogenicity of normal hepatic parenchyma increased after contrast agent administration, reaching a peak of about 250% (1DS) at 60 s and a decreasing gradually in 5 minutes. Conventional US detected 195 focal lesions, CT 231, and US with pulse inversion technique and contrast agent (US-PI) 287. Mean differences among the number of lesions detected by the different techniques per each patient were also calculated. Wilcoxon Signed Rank Test showed a statistically significant difference between US-PI and US (p < .0001), CT and US (p = .0052) and US-PI and CT (p = .0121). US-PI detected the smallest lesions, which went undetected by the CT and conventional US examinations. DISCUSSION AND CONCLUSIONS: In 10 cases (14.3%) contrast enhanced US-PI demonstrated the presence of a number of lesions greater than 5 (diffuse metastatization and inoperability) in comparison to that detected by spCT). The greater echogenicity of normal hepatic parenchyma using pulse inversion technique after Levovist infusion allowed to better demonstrate hepatic metastases. This technique showed a higher identification rate of small lesions in comparison to basal examination and to spiral CT. Contrast enhanced US-PI demonstrated a remarkable increase in echogenicity of hepatic parenchyma in portal phase. The technique significantly improves the detection of focal lesions allowing visualization of smaller lesions compared to CT and US. These results indicate that the technique could be used in the staging of liver metastasis. However, large multicentric trials are required to validate US-PI and better define its role in the work-up of patients with neoplastic disorder.

Adult↗
PubMed2001

Dynamic contrast enhanced magnetic resonance imaging subtraction in evaluating osteosarcoma response to chemotherapy.

PURPOSE: To evaluate the results of a new technique of dynamic contrast enhanced Magnetic Resonance (MR) imaging subtraction in the assessment of osteosarcoma response to chemotherapy. METHODS: 24 patients with high grade osteosarcoma, treated with preoperative neo-adjuvant chemotherapy, underwent MR at high field strength (1.5 T). Both unenhanced conventional SE T1- and T2-weighted sequences in the coronal and axial plane and dynamic Gd-DTPA-enhanced SE T1-weighted sequences in the coronal plane were performed. Image postprocessing included subtraction of unenhanced image from enhanced images (arbitrary called "angiographic subtraction") and subtraction of each enhanced image from the last-enhanced image (arbitrary called "pathologic area" subtraction). The early enhancing areas detected in the angiographic subtraction and the pathologic areas detected in the pathologic area subtraction were correlated with histopathological findings on histological macrosections obtained from the resected specimen. The sensitivity, specificity, accuracy, positive and negative predictive value of both the subtraction techniques were calculated. RESULTS: The early enhancing areas of angiographic subtraction were related not only to viable tumor but also to the host reactions such as flogosis and granulation tissue. The pathologic areas detected at the pathologic area subtraction correlated in most cases with viable tumor, while in 3 cases they did not correspond to viable tumor tissue and in 1 case a small area of residual viable tumor was missed. In assessing response to chemotherapy, pathologic areas subtraction had an accuracy of 95% (specificity: 100%, sensitivity: 93%, PPV: 100%, NPV: 88%), whereas angiographic subtraction had an accuracy of 79% (specificity: 37%, sensitivity: 100%, PPV: 76%, NPV: 100%). CONCLUSIONS: Pathologic area subtraction may be a useful technique for assessing the response of osteosarcoma to chemotherapy and for detecting residual viable tumor tissue.

Adolescent↗
PubMed2001

[Peripheral quantitative Computed Tomography (pQCT), broad ultrasound attenuation (BUA) and speed of ultrasound (SOS) in a normal population (426 females) aged 8 to 20 years].

PURPOSE: To evaluate, in a population of young healthy females aged from 8 to 20 years the bone mass peak (or density), the normal ranges versus age and menarche-age using two methods: pQCT (peripheral Quantitative Computed Tomography) and ultrasound absorptiometry. MATERIAL AND METHODS: From 1998 to 2000 selective measurement of Bone Mineral Density (BMD) of trabecular bone at the ultradistal radius using pQCT, BUA (Broad Band Attenuation) and SOS (Speed of Sound) was carried out on 426 healthy females (aged from 8 to 20 years) in north Italy. BMD was measured using a single photon miniaturized tomographic scanner in the ultradistal radius, SOS and BUA were measured at the same time, using a water bath device obtaining parametric bidimensional images of BUA and SOS. The population studied refers to normal females free of bone metabolism alteration, in pre and post-pubertal status. RESULTS: A normal range of BMD, BUA and SOS versus age and menarche age were established. A linear correlation was found between BUA and BMD measured with pQCT. SOS does not show any correlation with BMD. The pre-puberty and the post-puberty groups show statistically significative differences between SOS, BUA and BMD. We found the peak bone density (measured with pQCT) in the trabecular bone at the ultradistal radius at 15 years of age (mean menarche age of 10 years). The same position of the peak was found for BUA, for SOS the situation is not well defined. The analytical fitting of the data highlights a polynomial correlation of BMD vs. age, SOS vs. age, BUA vs. age. CONCLUSIONS: It appears that sexual growth influences the position of peak bone density. The results obtained show a statistically significant correlation between BUA and BMD and age, the menarche-age and the period of exposure of bone tissue to oestrogen. After all, pQCT and ultrasound are useful techniques to evaluate bone density and structure also in a growing population. The results of this study show that it is possible to use bidimensional quantitative ultrasound devices in clinical practice also in young populations taking in account age and sexual development.

Adolescent↗
PubMed2001

Maxillary sinus elevation: the effect of macrolacerations and microlacerations of the sinus membrane as determined by endoscopy.

The authors evaluated the health of the maxillary sinus in a group of 18 patients who had undergone sinus lift surgery for implantation purposes, using computed tomography and endoscopic imaging as a means of diagnosis. The study was performed after a mean interval of 31 months. All sinus lift operations were carried out using the lateral flap technique. The authors evaluated graft characteristics and intraoperative and postoperative complications and compared the results with computed tomography and endoscopic images. Endoscopy of a maxillary sinus that underwent microlaceration of the mucosa during sinus lifting showed a situation compatible with healthy conditions. In cases complicated by macrolaceration, the endoscopic picture was typical of sinusitis, even where clinical conditions of this type were not present. In the absence of intraoperative complications, the endoscopic appearance of sinus mucosa appears to improve when autologous graft material is used.

Adult↗
PubMed2000

Pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine derivatives as highly potent and selective human A(3) adenosine receptor antagonists: influence of the chain at the N(8) pyrazole nitrogen.

An enlarged series of pyrazolotriazolopyrimidines previously reported, in preliminary form (Baraldi et al. J. Med. Chem. 1999, 42, 4473-4478), as highly potent and selective human A(3) adenosine receptor antagonists is described. The synthesized compounds showed A(3) adenosine receptor affinity in the sub-nanomolar range and high levels of selectivity evaluated in radioligand binding assays at human A(1), A(2A), A(2B), and A(3) adenosine receptors. In particular, the effect of the chain at the N(8) pyrazole nitrogen was analyzed. This study allowed us to identify the derivative with the methyl group at the N(8) pyrazole combined with the 4-methoxyphenylcarbamoyl moiety at the N(5) position as the compound with the best binding profile in terms of both affinity and selectivity (hA(3) = 0.2 nM, hA(1)/hA(3) = 5485, hA(2A)/hA(3) = 6950, hA(2B)/hA(3) = 1305). All the compounds proved to be full antagonists in a specific functional model where the inhibition of cAMP generation by IB-MECA was measured in membranes of CHO cells stably transfected with the human A(3) receptor. The new compounds are among the most potent and selective A(3) antagonists so far described. The derivatives with higher affinity at human A(3) adenosine receptors proved to be antagonists, in the cAMP assay, capable of inhibiting the effect of IB-MECA with IC(50) values in the nanomolar range, with a trend strictly similar to that observed in the binding assay. Also a molecular modeling study was carried out, with the aim to identify possible pharmacophore maps. In fact, a sterically controlled structure-activity relationship was found for the N(8) pyrazole substituted derivatives, showing a correlation between the calculated molecular volume of pyrazolo[4,3-e]1,2, 4-triazolo[1,5-c]pyrimidine derivatives and their experimental K(i) values.

Animals↗
PubMed2000

Synthesis and biological effects of a new series of 2-amino-3-benzoylthiophenes as allosteric enhancers of A1-adenosine receptor.

New derivatives of PD 81,723, an allosteric enhancer of agonist binding to the A1-adenosine receptor, have been synthesized and evaluated in an intact cell assay. Compounds 3a, 3o and 3p appeared to be more potent than PD 81,723 and at a concentration of 0.1 microM caused significant reductions of cAMP content of CHO cells expressing the human A1-adenosine receptor. Compounds 4e and 4o appeared to be allosteric enhancers at a low concentration and antagonists at a higher concentration, whereas compounds 3c, 3g, 3s and 4l appeared to be weak antagonists that are also allosteric enhancers at the higher concentration of 10 microM.

Allosteric Regulation↗
PubMed2000

Synthesis and antitumor activity of new benzoheterocyclic derivatives of distamycin A.

The design, synthesis, and in vivo and in vitro antileukemic activity of a novel series of compounds (13-22 and 34), in which different benzoheterocyclic rings, bearing a nitrogen mustard or a benzoyl nitrogen mustard or an alpha-bromoacryloyl group as alkylating moieties, are tethered to a distamycin frame, are reported, and structure-activity relationships are discussed. The new derivatives were prepared by coupling nitrogen mustard-substituted, benzoyl nitrogen mustard-substituted, or alpha-bromoacryloyl-substituted benzoheterocyclic carboxylic acids 23-32 with desformyldistamycin (33) or in one case with its two-pyrrole analogue 35. With very few exceptions, the activities of compounds bearing the same alkylating moiety are slightly affected by the kind of the heteroatom present on the benzoheterocyclic ring. All novel compounds, with one exception, showed in vitro activity against L1210 murine leukemia cell line comparable to or better than that of tallimustine. The compounds in which the nitrogen mustard and the alpha-bromoacryloyl moieties are directly linked to benzoheterocyclic ring showed potent cytotoxic activities (IC(50) ranging from 2 to 14 nM), while benzoyl nitrogen mustard derivatives of benzoheterocycles showed reduced cytotoxic activities, and one compound (16) of this cluster was the sole derivative devoid of significant activity. Compound 18, a 5-nitrogen mustard N-methylindole derivative of distamycin, showed the best antileukemic activity in vivo, with a very long survival time (%T/C = 457), significantly increased in comparison to tallimustine (%T/C = 133), and was selected for further extensive evaluation. Arrested polymerase chain reaction and direct DNA fragmentation assays were performed for compound 18 and the structurally related compounds 13-17 and 19. The results obtained have shown that both alkylating groups and oligopeptide frames play a crucial role in the sequence selectivity of these compounds.

Acrylamides↗
PubMed2000

Synthesis of hybrid distamycin-cysteine labeled with 99mTc: a model for a novel class of cancer imaging agents.

The synthesis of a hybrid constituted by distamycin A and cysteine labeled with the gamma-emitting radionuclide 99mTc to afford the conjugate complex 5 is reported. This new radiopharmaceutical is of potential interest as tumor imaging agent in diagnostic nuclear medicine. The preparation of the hybrid distamycin A-cysteine 4 has been achieved by coupling deformyldistamycin A and Boc-Dmt-OH. Compound 4 was then successfully labeled with 99mTc by reaction with the novel, high-electrophilic, metal-containing fragment [99mTc(N)(PP)]2+ (PP = diphosphine ligand) yielding the 1:1 complex 5.

Cysteine↗
PubMed2000

Synthesis of conformationally constrained analogues of KN62, a potent antagonist of the P2X7-receptor.

Conformationally constrained analogues of KN62 containing 1,2,3,4-tetrahydro-7-hydroxyisoquinoline-3-carboxylic acid with S configuration in position 3 were synthesized and their antagonist activities were tested on human macrophage cells. While KN62 is a potent antagonist of the P2X7 receptor, these analogues were inactive as antagonists and only one compound showed appreciable activity as P2X7 antagonist, which was 30 times weaker than that reported for KN62.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2000

Synthesis and preliminary biological evaluation of [3H]-MRE 3008-F20: the first high affinity radioligand antagonist for the human A3 adenosine receptors.

The synthesis and the preliminary biological evaluation of the first high affinity radioligand antagonist for the human A3 adenosine receptor, named [3H]-MRE 3008-F20 are reported. [3H]-MRE 3008-20 bound human A3 receptors expressed in CHO cells with K(D) and Bmax value of 0.82 +/- 0.08 nM and 297 +/- 28 fmol/mg of protein, respectively. [3H]-MRE 3008-F20 represents a useful tool for a further characterization of A3 adenosine receptor subtype.

Animals↗
PubMed2000

A(3) adenosine receptor ligands: history and perspectives.

Adenosine regulates many physiological functions through specific cell membrane receptors. On the basis of pharmacological studies and molecular cloning, four different adenosine receptors have been identified and classified as A(1), A(2A), A(2B), and A(3). These adenosine receptors are members of the G-protein-coupled receptor family. While adenosine A(1) and A(2A) receptor subtypes have been pharmacologically characterized through the use of selective ligands, the A(3) adenosine receptor subtype is presently under study in order to better understand its physio-pathological functions. Activation of adenosine A(3) receptors has been shown to stimulate phospholipase C and D and to inhibit adenylate cyclase. Activation of A(3) adenosine receptors also causes the release of inflammatory mediators such as histamine from mast cells. These mediators are responsible for processes such as inflammation and hypotension. It has also been suggested that the A(3) receptor plays an important role in brain ischemia, immunosuppression, and bronchospasm in several animal models. Based on these results, highly selective A(3) adenosine receptor agonists and/or antagonists have been indicated as potential drugs for the treatment of asthma and inflammation, while highly selective agonists have been shown to possess cardioprotective effects. The updated material related to this field of research has been rationalized and arranged in order to offer an overview of the topic.

Animals↗
PubMed2000

Roux-en-Y jejunal loop and bile reflux.

BACKGROUND: The current opinion is that the reflux of jejunal juice over the whole length of a long Roux-en-Y jejunal loop is very uncommon. We aimed to challenge this concept by monitoring the presence of bile in the organ proximal to a 60-cm loop during a 24-hour period with use of the Bilitec device, an optoelectronic instrument capable of measuring absorbance of a beam of light, the wavelength of which is close to the absorbance peak of bilirubin. PATIENTS AND METHODS: Forty-one patients, 8 of whom had been cholecystectomized, were investigated after total gastrectomy (group I, n = 17), distal gastrectomy (group II, n = 7), or duodenal switch (group III, n = 17). The percentage of recording time absorbance >0. 25 (absorbance scale ranging from 0 to 1) was calculated in reference to data from healthy subjects. RESULTS: Bile was detected in 17 patients (41%), 5 belonging to group I, 2 to group II, and 10 to group III (P = 0.165). Bile exposure remained within the range of controls in 14 patients whereas it was above this range in 3 patients, 2 of whom had disabling heartburn and severe esophagitis. The percentage of time absorbance >0.25 did not significantly differ from one group to another (P = 0.257) or according to whether patients had been cholecystectomized or not (P = 0.439). However, unlike cholecystectomized patients, patients still having their gallbladder refluxed predominantly during postprandial periods. Lengthening of the loop from 60 cm to 110 cm in the 2 symptomatic patients with a pathologic bile reflux resulted in relief of heartburn and healing of esophagitis in both while bile reflux was abolished in 1 and dramatically reduced in the other. CONCLUSIONS: Bile refluxes over the whole length of 4 Roux-en-Y loops out of 10. In most patients, bile reflux remains within the range of healthy subjects, producing neither symptoms nor mucosal damage; and it occurs independently of the organ proximal to the loop, but its timing of occurrence is modified by cholecystectomy. Although only for exceptional indications, lengthening of an incompetent loop is effective in patients with excessive bile reflux and severe related symptoms and lesions.

Adult↗
PubMed2000

Human stomach has a recordable mechanical activity at a rate of about three cycles/minute.

OBJECTIVE: To discover whether the human stomach contracts every 20 seconds or not. DESIGN: Manometric study. SETTING: Teaching hospital, Belgium. SUBJECTS: 10 healthy volunteers, and 31 patients who had had the whole stomach denervated and pulled up to the neck for oesophageal replacement. INTERVENTIONS: Analysis of selected strips of manometric tracings obtained with intraluminal perfused catheters. 13 patients were given erythromycin (1g/day) by mouth. MAIN OUTCOME MEASURES: Estimation of the rate and frequency distribution according to amplitude of intraluminal pressure waves with the vertical axis of the tracings scaled up to reflect contractions within the gastric wall. RESULTS: Microwaves (<9 mmHg) that came in between conventional macrowaves (>9 mmHg) were found, showing that the human stomach undergoes mechanical activity (amplitude ranging from 0.2-310 mmHg) at the pacemaker's rate which varied from 2.43 to 3.60 cycles/minute from one subject to another. Phase I of the interdigestive motor complex contained microwaves only, phase II and the fed pattern consisted of a mixture of microwaves and macrowaves, and phase III contained macrowaves only. The fasting rate of mechanical activity was lower in patients who were given erythromycin than in those not given erythromycin (p = 0.003) and in healthy volunteers (p = 0.002), and it increased significantly after a meal (p < 0.0001). Microwaves in strips in which they were the most prominent were of higher amplitude in patients than in healthy volunteers (median: 3.5 compared with 2.5 mmHg; p < 0.0001). CONCLUSIONS: The human stomach has mechanical activity at the rate at which the pacemaker generates electrical slow waves. The classic phases of the gastric motor activity seem to differ from each other by the frequency distribution of pressure waves according to amplitude rather than by the contraction rate. Weak mechanical activity is much more readily detectable after the stomach has been denervated and tailored for oesophageal substitution.

Abdominal Muscles↗
PubMed2000

[2,1-c][1,4]benzodiazepine (PBD)-distamycin hybrid inhibits DNA binding to transcription factor Sp1.

We designed and synthesized the hybrid 6, prepared combining the minor groove binders distamycin A and pyrrolo [2,1-c][1,4] benzodiazepine (PBD) 4, related to the natural occurring anthramycin (2) and DC-81 (3). In this paper, the effects of the compound 6 on molecular interactions between DNA and transcription factor Sp1 were studied. The results obtained demonstrate that PBD-distamycin hybrid is a powerful inhibitor of Sp1/DNA interactions.

Animals↗
PubMed2000

In vivo lipid peroxidation and platelet activation in cystic fibrosis.

F(2)-isoprostanes are bioactive peroxidation products of arachidonic acid whose urinary excretion provides an index of lipid peroxidation in vivo. We tested the hypothesis that formation of F(2)-isoprostanes is altered in patients with cystic fibrosis and contributes to platelet activation and pulmonary dysfunction in this setting. The urinary excretion of immunoreactive 8-iso-prostaglandin F(2alpha) (PGF(2alpha)) was significantly (p = 0.0001) higher in 36 patients with cystic fibrosis than in 36 age-matched healthy subjects: 618 +/- 406 versus 168 +/- 48 pg/mg creatinine. The urinary excretion of immunoreactive 11-dehydro-thromboxane B(2) (TXB(2)), an index of in vivo platelet activation, was also significantly (p = 0.0001) higher in patients than in control subjects: 2,440 +/- 1,453 versus 325 +/- 184 pg/mg creatinine. The excretion rate of 8-iso-PGF(2alpha) was correlated with that of 11-dehydro-TXB(2) (rho = 0.51; p = 0.0026) and inversely related to FEV(1) (rho = -0.40; p = 0.0195). Urinary 8-iso-PGF(2alpha) excretion was largely unaffected during cyclooxygenase inhibition with low-dose aspirin, nimesulide, or ibuprofen, consistent with a noncyclooxygenase mechanism of F(2)-isoprostane formation in cystic fibrosis. Increased vitamin E supplementation (from 200 to 600 mg/d) was associated with statistically significant (p = 0.005) reductions in urinary 8-iso-PGF(2alpha) and 11-dehydro-TXB(2) excretion, by 42% and 29%, respectively. We conclude that enhanced lipid peroxidation is an important feature of cystic fibrosis and may contribute to persistent platelet activation and pulmonary dysfunction via generation of bioactive isoeicosanoids. Our results provide a rationale for reassessing the adequacy of vitamin E supplementation in this setting.

Adolescent↗