BACKGROUND: Pouchitis is the major long-term complication after ileal pouch-anal anastomosis for ulcerative colitis. About 15% of patients have a chronic, treatment-resistant disease. AIMS: To evaluate the efficacy of an antibiotic combination for chronic active, treatment-resistant pouchitis. PATIENTS AND METHODS: Eighteen patients were treated orally with rifaximin 1 g b.d. + ciprofloxacin 500 mg b.d. for 15 days. Symptoms assessment, endoscopic and histological evaluations were performed at screening and after 15 days using the Pouchitis Disease Activity Index (PDAI). Improvement was defined as a decrease of at least 3 points in PDAI score, and remission as a PDAI score of 0. Systemic absorption of rifaximin was determined by high performance liquid chromatography. Faecal samples were collected before and after antibiotic treatment for stool culture. RESULTS: Sixteen out of 18 patients (88.8%) either improved (n=10) or went into remission (n=6); the median PDAI scores before and after therapy were 11 (range 9-17) and 4 (range 0-16), respectively (P < 0.002). No side-effects were reported. Rifaximin plasma levels and urinary excretion were negligible, confirming its mainly topical activity. A significant decrease in total anaerobes and aerobes, enterococci, lactobacilli, bifidobacteria and bacteroides in faecal samples was observed, while the reduction in number of coliforms and Clostridium perfringens did not reach a statistical significance. CONCLUSIONS: A combination of rifaximin and ciprofloxacin was effective in patients with active chronic, treatment-resistant pouchitis, suggesting the need, in these patients, for treatment using antibiotic agents with wide antibacterial spectrum of activity.

Adult↗

PubMed1999

Impact on the composition of the faecal flora by a new probiotic preparation: preliminary data on maintenance treatment of patients with ulcerative colitis.

BACKGROUND: Although 5-aminosalicylic acid (5-ASA) oral compounds are the standard maintenance treatment for ulcerative colitis in remission, some patients cannot use them because of side-effects. Clinical and experimental observations have suggested the potential role of probiotics in inflammatory bowel disease therapy. AIM: To evaluate the effects on intestinal microflora and the clinical efficacy of a new probiotic preparation in patients with ulcerative colitis in remission. PATIENTS AND METHODS: Twenty patients with ulcerative colitis, intolerant or allergic to 5-ASA, have been treated with a new probiotic preparation (VSL#3, CSL, Milan, Italy) containing 5x10(11) cells/g of 3 strains of bifidobacteria, 4 strains of lactobacilli and 1 strain of Streptococcus salivarius ssp. thermophilus. Two doses of 3 g were administered o.d. for 12 months. Faecal samples for stool culture were obtained from the patients at the beginning of the trial and after 10, 20, 40, 60, 75, 90 days, 12 months and at 15 days after the end of the treatment. The following bacterial groups have been evaluated in the faeces: total aerobic and anaerobic bacteria, enterococci, Streptococcus thermophilus, lactobacilli, bifidobacteria, Bacteroides, clostridia, coliforms. Patients were assessed clinically every two months, and assessed endoscopically at 6 and 12 months or in relapse. RESULTS: Faecal concentrations of Streptococcus salivarius ssp. thermophilus, lactobacilli and bifidobacteria increased significantly in all patients, compared to their basal level, from the 20th day of treatment (P<0.05) and remained stable throughout the study. Concentrations of Bacteroides, clostridia, coliforms, total aerobic and anaerobic bacteria did not change significantly during treatment (P = N.S.). Fifteen of 20 treated patients remained in remission during the study, one patient was lost to follow up, while the remaining relapsed. No significant side-effects have been reported. CONCLUSIONS: These results show that this probiotic preparation is able to colonize the intestine, and suggest that it may be useful in maintaining the remission in ulcerative colitis patients intolerant or allergic to 5-ASA. Controlled trials are warranted to confirm these preliminary results.

Adult↗

PubMed1999

Effect of cardiac exposure by median sternotomy on atrial fibrillation cycle length.

BACKGROUND: Epicardial mapping is a powerful tool that has enabled us to gain insight into the electrical phenomena perpetuating atrial fibrillation and has guided the design of surgical and catheter-based therapeutic strategies. However, epicardial data are acquired during abnormal physiological conditions; the patients are anaesthetized, their chests opened, dislocating the heart and exposing it to air of room temperature, and the autonomic tone is modulated due to the surgery. The effect of intra-operative conditions on atrial electrophysiological properties have not been investigated before. Thus in the present study we assessed the atrial cycle length, shown to be an index of atrial refractoriness, and the ventricular rate before and during open-heart surgery in 10 patients with chronic atrial fibrillation and an underlying heart disease. METHODS AND RESULTS: Using a newly introduced and validated ECG method known as frequency analysis of fibrillatory ECG (FAF-ECG), the atrial cycle length and the ventricular rate were determined just before surgery. After anaesthesia and median sternotomy, epicardial mapping of the entire right atrial free wall was performed. The mean ventricular rate as well as the dominant atrial fibrillation cycle length consistently increased, the former from 71 to 92 beats x min(-1) (mean of all patients, P<0.05) and the latter from 156 to 172 ms (P<0.05). CONCLUSIONS: Atrial fibrillation cycle length, an index of atrial refractoriness, is increased as an effect of anaesthesia and heart exposure during open-heart surgery in patients with chronic atrial fibrillation, implying that atrial activation might be altered, which must be considered when interpreting data from epicardial conduction analysis.

Aged↗

PubMed1998

Comparison of different labelling index formulae used on bromodeoxyuridine-flow cytometry data.

The essence of the bromodeoxyuridine (BrdUrd)-flow cytometry (FCM) technique is that cells are labelled with the thymidine analogue BrdUrd. They are then allowed to progress through the cell cycle in a BrdUrd-free environment during the postlabelling time period. At a postlabelling time shorter than the length of the S phase (Ts), cells are fixed and prepared for FCM-mediated analysis of BrdUrd and DNA contents. From FCM-derived data, cell cycle kinetic parameters such as labelling index (LI), Ts, and potential doubling time (Tpot) can be calculated. Tpot is believed to be important in the evaluation of tumor aggressiveness and therapy response. Since LI is most commonly used together with Ts to calculate Tpot, it is important that both LI and Ts are independent of the time when cells are sampled. Several formulae to calculate LI and Ts have been presented. In the present paper, we deal with various formulae to calculate LI. These formulae differ in how they take into account unlabelled and BrdUrd-labelled cells in various fractions of the cell cycle. We present a new formula, which takes into consideration cells in the different fractions and thus makes LI theoretically independent of postlabelling time. Our results show that different LI values are obtained when different formulae are used to calculate LI. In addition, we show that the BrdUrd labelling period should be kept as short as possible.

Animals↗

PubMed1998

Analysis of adaptation in anteroposterior dynamics of human postural control.

To quantify the postural adjustments over time, twelve normal subjects were investigated with posturography during vibration either toward the calf or the paraspinal neck muscles; with eyes open vs. eyes closed. The stimulus response adjustments over time were found to be almost identical for all test conditions, though the responses were smaller during eyes open conditions. To determine the response adjustments and thus the dynamics of postural control, a system identification methodology incorporating both step response and dynamic feedback components was developed. This methodology can be used to quantify both short-term stimulus response and postural adaptive adjustments when evaluating postural control performance. Copyright 1998 Elsevier Science B.V.

Journal Article↗

PubMed1998

Non-invasive assessment of the atrial cycle length during atrial fibrillation in man: introducing, validating and illustrating a new ECG method.

OBJECTIVES: Atrial fibrillation (AF) in man has previously been shown to include a wide variety of atrial activity. Assessment of the characteristics of this arrhythmia with a commonly applicable tool may therefore be important in the choice and evaluation of different therapeutic strategies. As the AF cycle length has been shown to correlate locally with atrial refractoriness and globally with the degree of atrial organization, with, in general, shorter cycle length during apparently random AF compared to more organized AF, we have developed a new method for non-invasive assessment of the AF cycle length using the surface and the esophagus (ESO) ECG. METHODS AND RESULTS: From the frequency spectrum of the residual ECG, created by suppression of the QRST complexes, the dominant atrial cycle length (DACL) was derived. By comparison with multiple intracardiac simultaneously acquired right and left AF cycle lengths in patients with paroxysmal AF, we found that the DACL in lead V1, ranging from 130 to 185 ms, well represented a spatial average of the right AF cycle lengths, whereas the DACL in the ESO ECG, ranging from 140 to 185 ms, reflected both the right and the left AF cycle length, where the influence from each structure depended on the atrial anatomy of the individual, as determined by MRI. In patients with chronic AF, the method was capable of following changes in the AF cycle length due to administration of D,L-sotalol and 5 min of ECG recording was sufficient for the DACL to be reproducible. CONCLUSIONS: We conclude that this new non-invasive method, named 'Frequency Analysis of Fibrillatory ECG' (FAF-ECG), is capable of assessing both the magnitude and the dynamics of the atrial fibrillation cycle length in man.

Adult↗

PubMed1998

2-aminotetralin-derived substituted benzamides with mixed dopamine D2, D3, and serotonin 5-HT1A receptor binding properties: a novel class of potential atypical antipsychotic agents.

A new chemical class of potential atypical antipsychotic agents, based on the pharmacological concept of mixed dopamine D2 receptor antagonism and serotonin 5-HT1A receptor agonism, was designed by combining the structural features of the 2-(N,N-di-n-propylamino)tetralins (DPATs) and the 2-pyrrolidinylmethyl-derived substituted benzamides in a structural hybrid. Thus, a series of 35 differently substituted 2-aminotetralin-derived substituted benzamides was synthesized and the compounds were evaluated for their ability to compete for [3H]-raclopride binding to cloned human dopamine D2A and D3 receptors, and for [3H]-8-OH-DPAT binding to rat serotonin 5-HT1A receptors in vitro. The lead compound of the series, 5-methoxy-2-[N-(2-benzamidoethyl)-N-n-propylamino]tetralin (12a), displayed high affinities for the dopamine D2A receptor (Ki = 3.2 nM), the dopamine D3 receptor (Ki = 0.58 nM) as well as the serotonin 5-HT1A receptor (Ki = 0.82 nM). The structure-affinity relationships of the series suggest that the 2-aminotetralin moieties of the compounds occupy the same binding sites as the DPATs in all three receptor subtypes. The benzamidoethyl side chain enhances the affinities of the compounds for all three receptor subtypes, presumably by occupying an accessory binding site. For the dopamine D2 and D3 receptors, this accessory binding site may be identical to the binding site of the 2-pyrrolidinylmethyl-derived substituted benzamides.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1998

Right atrial free wall conduction velocity and degree of anisotropy in patients with stable sinus rhythm studied during open heart surgery.

AIMS: Although the perpetuation of several supraventricular arrhythmias is critically dependent upon intra-atrial conduction, the literature lacks detailed information on normal values of conduction velocity and degree of anisotropy. In order to explore these factors further, we have measured conduction velocities at the right atrial free wall during sinus rhythm and during atrial pacing in four directions parallel and perpendicular to the atrioventricular groove in patients with normal atria and stable sinus rhythm. METHODS AND RESULTS: Using a Bard Cardiac Mapping System, atrial ECGs were recorded using a 3 x 4 cm electrode array with 56 equally spaced bipolar electrodes in 12 patients undergoing open heart surgery due to ischaemic heart disease or Wolf-Parkinson-White syndrome. A bipolar pen probe connected to a Medtronic 5328 stimulator was used for pacing at a 10% higher rate than sinus rhythm. The local activation times were manually set and isochronal activation maps were created for each recording. The conduction velocities were calculated from the activation maps over a distance ranging from 2.2 to 4.2 cm. The majority of the activation maps showed no signs of anisotropy; the others had less than 15% spatial inhomogeneity of conduction. Mean conduction velocity, calculated from five consecutive beats, was 88 +/- 9 cm.s-1 (mean +/- SD), ranging between 68 +/- 4 and 103 +/- 3 cm.s-1 during sinus rhythm. Mean conduction velocity during atrial pacing was 81 +/- 16 cm.s-1 at a propagation direction of 0 degree, 74 +/- 14 cm.s-1 at a 90 degrees direction, 79 +/- 12 cm.s-1 at 180 degrees and 78 +/- 20 cm.s-1 at 270 degrees, where 0 degree was parallel to the atrioventricular groove in the cranial direction and the angle increased counter-clockwise. Mean conduction velocity during sinus rhythm was significantly higher (P < 0.05) than during atrial pacing at the 90 degrees and 180 degrees directions but not compared to atrial pacing at 0 degree or 270 degrees. There was no significant difference in mean conduction velocity in different directions during atrial pacing. CONCLUSION: Although anisotropy was documented during conduction velocity in individual cases, conduction velocity was not dependent on propagation direction at the epicardial right atrial free wall in patients with stable sinus rhythm. These findings do not exclude the presence of internodal preferential pathways as these are located sub-epicardially and a marked transmural discordance in activation has previously been documented in the vicinity of such pathways.

Adult↗

PubMed1998

Azaserine-induced rat pancreas tumor model with transplantable cultured cells.

The purpose of this study was to describe the inoculation technique and patterns of growth as well as to characterize typical histological features of Lewis rat subcutaneous and intrapancreatic tumors, induced by inoculation of cultured pancreatic cancer cells (DSL-6A/C1). Subcutaneous inoculation of cultured cells produced a solid tumor that was a locally invasive, well- to moderately differentiated ductal adenocarcinoma. Tumor take was 100% in animals 5 weeks of age; tumor growth was consistent and predictable and a tumor volume of approximately 1 cm3 was reached in 8 weeks. After intrapancreatic transplantation the tumors showed the same histological features as subcutaneous tumors. During inoculation carcinoma cells easily spread around the injected area, and after 2 weeks both pancreatic tumors and superficially infiltrating carcinomas were found in the liver and spleen and around the peritoneum. Tumor take was 60% and tumor growth was somewhat indefinite and unpredictable in the pancreas. However, by reducing the injected carcinoma cell volume and solving the technical problems, 100% tumor take was achieved. The tumor volume reached 2 mm3 during 2 weeks and larger tumors showed a tendency for invasion. According to our results, subcutaneous as well as intrapancreatic tumor induction with cultured cells offers a model for pancreatic cancer studies.

Adenocarcinoma↗

PubMed1998

[Primary malignant melanoma of the larynx].

Explore the source record for details and available documents.

Aged↗

PubMed1997

New progeroid disorder.

We report on a 10-year-old Caucasian male with a prematurely aged appearance, delayed bone maturation and dental development, pronounced acro-osteolysis with brachydactyly, and distinctive cutaneous findings including hard, confluent skin lesions with some clinical and histologic resemblance to those of juvenile hyaline fibromatosis (JHF). He also had hyperopia, sensorineural hearing loss, and elevated TSH. Linear growth and intellectual functions were normal. We believe that this patient represents a new progeroid disorder.

Abnormalities, Multiple↗

PubMed1997

Epicardial right atrial free wall mapping in chronic atrial fibrillation. Documentation of repetitive activation with a focal spread--a hitherto unrecognised phenomenon in man.

BACKGROUND: Previous studies have shown that atrial fibrillation of recent onset in man is based on a varying number of simultaneously present activation waves reentering either themselves or each other. In the present study, right atrial activation during chronic atrial fibrillation in man was studied. METHODS AND RESULTS: In 16 patients with chronic atrial fibrillation multiple epicardial recordings of 8 s each were made at the right atrial posterior free wall and at the appendage using a 20 x 35 mm electrode array with 56 bipolar measurement points. The preferable activation pattern of each recording and the propagation direction, cycle length and conduction velocity of individual activation waves within each recording were determined. Activation was characterized by unorganised activation with several simultaneously present activation waves: inconsistent preferable activation pattern (n = 5), predominantly organised activation with either frequent episodes of uniform activation: consistent preferable activation pattern (n = 7) or frequent episodes of activation with focal spread; focal preferable activation pattern (n = 4). Random re-entry was frequently documented in recordings with the inconsistent preferable activation pattern and less frequently in recordings with the consistent and focal preferable activation pattern. Complete re-entry circuits were rarely documented. The median fibrillation cycle length was 146, 159 (P < 0.05) and 165 ms (not significant) and the mean conduction velocity during uniform activation was 64, 67 and 83 cm. s-1 (not significant) in recordings with the inconsistent, consistent and focal preferable activation pattern, respectively. CONCLUSIONS: During chronic atrial fibrillation in man, right atrial free wall activation ranges from disorganised activation with multiple co-existing activation waves to predominantly organised activation characterized by either uniform activation consistent with the presence of large re-entry circuits or repetitive activation of unknown mechanism and focal spread.

Aged↗