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Secondary interventions following endovascular repair of abdominal aortic aneurysm.

PURPOSE: To review the outcomes of endovascular abdominal aortic aneurysm repair (EVAR) procedures, to determine the incidence of adverse events, and to assess the need for secondary radiological/surgical interventions. MATERIALS AND METHODS: Data from 57 consecutive patients entered in a prospective EVAR database were studied. In addition to database interrogation, case notes and radiology records were reviewed. Frequency and outcome of complications were evaluated after stent-graft placement (mean follow up 20 months). RESULTS: Overall, 24 adverse events were recorded in 57 patients (42%). The events were endoleaks (14/24), stent migrations (3/24), deployment problems (2/24), limb occlusions (2/24), limb kink (1/24), and femoro-femoral crossover occlusions (2/24). Of all the endovascular patients studied, 23% (13/57) required secondary interventions to maintain aneurysm exclusion. The mean time to secondary intervention in this series was 14 months. CONCLUSION: Over 40% of EVAR procedures were associated with suboptimal clinical outcomes, and more than 20% of the patients required secondary interventions within 5 years of surgery. This high incidence of late secondary intervention is a cause for concern and emphasizes the need for lifelong follow-up.

Aged↗

[Comparison of the effects of depot isosorbide dinitrate (Isoket Retard 120) and diltiazem in patients with exertional angina pectoris].

In a simple blind crossover 7-week study with a randomized beginning the authors compared in 13 patients with stable angina pectoris after exercise the action of diltiazem (Blocalcin 60, Lachema) and isosorbidedi nitrate (Isoket retard 120, Schwarz). Both drugs improved significantly, as compared with placebo, the tolerance of the load, reduced the frequency of stenocardias per 24 hours, diltiazem also the nitroglycerin consumption per 24 hours. Diltiazem reduced significantly, as compared with isosorbidedi nitrate, the pulse rate at rest, it reduced significantly Robinson's index and the diastolic pressure at rest. In none of the other investigated parameters there was a significant difference between the two drugs and both are valuable in the treatment of angina after exercise. Diltiazem was well tolerated by the patients, while headache was a frequent side-effect of isosorbide dinitrate.

Adult↗

[RecE-independent recombination of plasmids in Bacillus subtilis cells].

The pUB110 and pE194 plasmid cointegrates have been isolated and examined in rec+ and recE4 strains of Bacillus subtilis. Cointegrates were shown to be formed by recombination at the specific site present on both parental plasmids as a short region of homology designated RSA. The RSA consists of 63 nucleotides in pE194 and 49 in pUB110; the length of its fully conserved core segment is 10 nucleotides. All cointegrates examined were formed by single crossover event taking place within the core segment, and as a result they have identical nucleotide sequences of recombination junctions. No conversion of mismatched base pairs to nucleotide sequences originally belonging to one of the parental plasmids was found. Though the action of RecE gene did not affect the frequency of cointegrate formation, it was reduced in rec149 host by one order of magnitude. Cointegrates retained their stability during transformation.

Bacillus subtilis↗

The efficacy and safety of probiotic Lactobacillus rhamnosus GG on prolonged, noninfectious diarrhea in HIV Patients on antiretroviral therapy: a randomized, placebo-controlled, crossover study.

PURPOSE: The aim of this placebo-controlled, crossover study was to evaluate the efficacy and safety of probiotic Lactobacillus rhamnosus GG (LGG) in ameliorating gastrointestinal symptoms in HIV-infected patients on antiretroviral therapy. METHOD: Infectious causes for diarrhea (bacteria, ova, parasites, and viruses including cryptosporidium, microsporidia, and cyclospora) were excluded with fecal samples before the study. HIV-infected patients with diarrhea for more than 1 month received in randomized order probiotic LGG preparation (containing viable LGG 1-5 x 1010 cfu/dose) and placebo twice a day for 2 weeks. Gastrointestinal symptoms were assessed daily and included the daily number of bowel movements, classification of stool consistency (watery, semi-watery, loose, firm, or foaming), and Visual Analog Scale (VAS) of gastrointestinal symptoms (flatulence, stomach pain, bloating disorders, general well-being). RESULTS: Seventeen HIV-infected patients completed the study. There were no significant differences between the treatment groups in the frequency or the consistency of diarrhea. In the VAS assessments of gastrointestinal symptoms, no difference between LGG and placebo could be detected. No adverse events were reported. The number of HIV RNA copies in the blood and CD4 cell counts remained stable during the study. CONCLUSION: Probiotic LGG preparation was well-tolerated in HIV infected patients. No significant differences in noninfectious diarrhea or gastrointestinal symptoms compared to placebo could be observed in this crossover study.

Adult↗

High frequency repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex in schizophrenic patients.

Repetitive transcranial magnetic stimulation (rTMS) has been tried therapeutically in major depression. In order to investigate the therapeutic efficacy of rTMS in psychotic patients, 12 participants (four women, eight men) with schizophrenia according to DSM-IV criteria, aged 25 to 63 years (mean (+/-s.d) 40.4+/-11.0), were enrolled in the study. Following a double-blind crossover design, patients were treated at random with 2 weeks of daily left prefrontal rTMS (20 2s 20 Hz stimulations at 80% motor threshold over 20 min, dorsolateral preforntal cortex) and 2 weeks of sham stimulation. The Brief Psychiatric Rating Scale decreased under active rTMS (p <0.05), whereas depressive symptoms (BDI) and anxiety (STAI) did not change significantly. Prefrontal rTMS might be effective in the non-pharmacological treatment of psychotic patients.

Adult↗

Usefulness and safety of cimetidine in patients receiving mexiletine for ventricular arrhythmia.

Cimetidine, a commonly used H2 receptor antagonist, was found to adversely interact with many drugs metabolized by the liver, including class I antiarrhythmic agents, lidocaine and quinidine. Mexiletine is a new class I antiarrhythmic agent similar to lidocaine which when used orally may have significant gastric side effects. Since some patients with peptic ulcer disease or gastric hyperacidity on mexiletine may benefit from the addition of cimetidine, it was important to rule out any significant adverse interaction between the two drugs in such patients. Eleven patients currently receiving long-term oral mexiletine for the treatment of complex ventricular arrhythmia underwent a double-blind crossover trial where they were maintained on their usual dose of mexiletine, and cimetidine, 300 mg orally every 6 hours, or placebo were added for a 1-week period each. Peak and trough mexiletine blood levels were not significantly altered by cimetidine. Similarly, there was no significant change in the frequency and severity of ventricular arrhythmia when cimetidine was added to mexiletine. Cimetidine reduced gastric side effects of mexiletine in 50% of patients who had complained of such symptoms on mexiletine alone or on mexiletine and placebo. We conclude that cimetidine can effectively reduce gastric side effects of mexiletine in many patients without adversely affecting the plasma concentration or the efficacy of the drug.

Aged↗

Thromboxane antagonism and cough induced by angiotensin-converting-enzyme inhibitor.

BACKGROUND: The increased prostaglandin synthesis that might follow stimulation of the arachidonic acid cascade by angiotensin-converting-enzyme inhibition (ACE-I) has been suggested to underlie the appearance of cough on ACE-I treatment. We investigated whether the prostanoid thromboxane was involved. METHODS: Nine patients with essential hypertension who had cough after enalapril 20 mg once a day (coughers) were treated, while continuing the enalapril, in a double-blind crossover study with placebo or picotamide, 600 mg twice daily. Picotamide is a platelet antiaggregant that acts through both inhibition of thromboxane synthase and thromboxane-receptor antagonism. Thirteen hypertensive patients with no history of ACE-I-induced cough were also treated with enalapril and served as controls. Cough frequency was measured by a visual analogue scale and by a daily cough diary. 24 h urinary recovery of 11-dehydro-thromboxane-B2 and 6-keto-PGF1 alpha were measured to assess any changes in endoperoxide metabolism during the study periods. FINDINGS: 11-dehydro-thromboxane-B2 (TXB2) recovery was significantly reduced by picotamide, which led to the disappearance of cough in eight patients within 72 h. Picotamide urinary recovery data suggested incomplete absorption in the non-responder. At baseline and after rechallenge with enalapril, 11-dehydro-TXB2 excretion was in the same range in the controls and in the coughers, but the latter showed significantly lower excretion of 6-keto-PGF1 alpha, and their ratio of 11-dehydroTXB2 to 6-keto-PGF1 alpha was twice that of the controls (1.40 [95% CI 0.86-1.95] vs 0.61 [0.37-0.84]). INTERPRETATION: A thromboxane antagonist is effective in ACE-I-induced cough. An imbalance between thromboxane and prostacyclin may represent a marker of patients susceptible to ACE-I-induced cough.

6-Ketoprostaglandin F1 alpha↗

Quantitative analysis of the electroencephalogram during cranial electrotherapy stimulation.

OBJECTIVE: Normal individuals were used to quantitate electroencephalographic (EEG) changes during concurrent administration of 0.5 and 100 Hz cranial electrotherapy stimulation (CES). METHODS: Twelve normal, right-handed males were used in a randomized, double-blind crossover design study. A 3 amplifier system incorporating noise-cancellation was used to collect one channel of EEG (O1-Cz configuration) for 30 min. Either 0.5, 100 Hz, or sham CES treatment was administered for 20 min of each session. Statistical analyses were applied to time- and frequency-domain EEG variables. RESULTS: Relative to sham control, 0.5 and 100 Hz CES caused the alpha band mean frequency to shift downward. Additionally, 100 Hz CES also caused a decrease of the alpha band median frequency and beta band power fraction. CONCLUSIONS: Both 0.5 and 100 Hz CES provide frequency distribution shifts that suggest beneficial changes in mental state. However, compared to 0.5 Hz CES, 100 Hz CES effected a greater overall change. It is suggested that similar tests be performed on individuals with various behavioral and neurological disorders to determine if comparable EEG changes can be realized and correlated with beneficial effects of CES therapy.

Adult↗

Crossing over as assessed by late recombination nodules is related to the pattern of synapsis and the distribution of early recombination nodules in maize.

Recombination nodules (RNs) are multicomponent proteinaceous ellipsoids found in association with the synaptonemal complex (SC) during prophase I of meiosis. Numerous early RNs (ENs) are observed during zygotene, and they may be involved in homologous synapsis and early events in recombination. Fewer late RNs (LNs) are observed during pachytene, and they occur at crossover sites. Here we describe the pattern of synapsis and the distribution of ENs and LNs in maize. Synapsis starts almost exclusively at chromosome ends, although later in zygotene there are many interstitial sites of synaptic initiation. ENs do not show interference, except possibly at distances < or = 0.2 micron. The frequency of ENs is higher on distal compared to medial SC segments, and the highest concentration of ENs occurs at synaptic forks. The number of ENs on an SC segment does not change during zygotene. These observations are interpreted to indicate that ENs are assembled at synaptic forks. Like ENs, LNs are more concentrated distally on bivalents but, unlike ENs, LNs show interference. A model is presented that relates the pattern of synapsis and ENs to the pattern of late nodules and crossing over.

Crossing Over, Genetic↗

Double-blind, crossover, placebo-controlled trial of bromocriptine in patients with sleep bruxism.

This study was designed to assess the effects of bromocriptine, a dopamine D2 receptor agonist, on sleep bruxism. Seven otherwise healthy patients with severe and frequent sleep bruxism participated in this randomized, double-blind, placebo-controlled study. The study used a crossover design that included 2 weeks of active treatment or placebo with a washout period of 1 week. To further evaluate whether bromocriptine influences striatal D2 receptor binding, we used iodine-123-iodobenzamide single photon emission computed tomography (SPECT) under both placebo and bromocriptine regimens. Bromocriptine did not reduce the frequency of episodes of bruxism during sleep (mean +/- SEM, 9.0 +/- 1.0 and 9.6 +/- 1.5 bruxism episodes per hour for placebo and bromocriptine, respectively) or the amplitude of masseter muscle contractions (root mean square values, 48.2 +/- 15.5 microV and 46.9 +/- 12.7 microV for placebo and bromocriptine, respectively). SPECT also failed to reveal that either treatment had any influence on striatal D2 binding (values for total binding in counts/pixel, 1.80 [1.72-1.93] and 1.79 [1.56-1.87] for placebo and bromocriptine, respectively). This study shows that a nightly dose of bromocriptine does not exacerbate or reduce sleep bruxism motor activity.

Adult↗

Controlled release carbamazepine: cognitive side effects in patients with epilepsy.

The treatment of epilepsy with carbamazepine (CBZ) may be hampered by cognitive side effects. These side effects are thought to be related to pharmacokinetic properties of the drug. The serum concentration of CBZ is characterized by rapid absorption and a short half-life, which may lead to a considerable fluctuation of the level between doses. Cognitive defects may result from peak levels: short periods with high serum concentration. In a single-blind crossover design, cognitive performance was compared in three conditions. All patients were first tested in the steady state of conventional CBZ. The patients were then assigned randomly to either CBZ-controlled release (CR) or a condition in which conventional CBZ was administered in the same tablet form and dose frequency as CR. Psychological tests were administered four times daily, immediately after the serum samples were taken. A nonmedication control group was tested following the same test scheme to obtain standards for the evaluation of changes in performance during the day. A systematic tendency was found toward higher test performance in the CR condition. This is especially evident for tests of memory and accuracy of visual information processing. The results of the repeated test procedure show that the smoothing effect of the CR condition on serum concentration fluctuations results in a more stable pattern of cognitive functioning during the day.

Adolescent↗

Sleep and wake after benzodiazepine hypnotics: a 20-hour EEG comparison of lormetazepam and flunitrazepam.

In an electropharmacokinetic study, the effects of lormetazepam and flunitrazepam were compared by the means of a sleep EEG and waking EEG during the following daytime. At a 1-week interval, 6 normal subjects received at random either 2 mg lormetazepam or 2 mg flunitrazepam in a double-blind, crossover fashion. Sleep EEG was recorded throughout the night; 6-min EEG samples were recorded every hour during 10 hours on the following daytime for spectral analysis. Night sleep after flunitrazepam showed lower Stage IV sleep than after lormetazepam. During daytime, only flunitrazepam induced an increased percentage of beta 2 frequencies, which remained above baseline up to 10 hours after awakening, indicating a prolonged impregnation time. This study permitted comparison of the relative intensity and duration of these two benzodiazepines: lormetazepam appeared to be a short-acting hypnotic while flunitrazepam displayed longer modification of the brain electrical activity.

Adult↗

Forced use treatment of childhood hemiparesis.

OBJECTIVE: Forced use, or constraint-induced, movement therapy has shown some efficacy in the rehabilitation of adults with chronic hemiparesis as a result of stroke. We used restraint of the unimpaired arm to ascertain whether this would improve function of the paretic arm in children with chronic (>1 year) hemiparesis. METHODS: Twelve hemiparetic treatment children (age 1-8 years) received a plaster cast on the unimpaired arm for 1 month; 13 hemiparetic control children did not. Peabody Developmental Motor Scales (PDMS) were performed on all treatment and control children immediately before and after casting and again 6 months later when controls crossed over to receive casts. Thus, PDMS were performed at entry, then 1 month, 6 months, and 7 months after entry. Any noted change in functional ability was also elicited by parental report. The frequency of visits to physical and occupational therapy was recorded. RESULTS: The 12 treatment (casted) children improved 12.6 PDMS points after 1 month of casting; the 13 control children improved 2.5 points. Improved PDMS scores persisted 6 months later when 7 treatment children returned. Similar results were obtained in the crossover when 10 control children received casts. Parental report corroborated improvement in casted children (22 of 22 parents) and its persistence at follow-up (21 of 22 parents). Receiving ongoing physical/occupational therapy did not seem to account for these results: control children received more (2.1 visits/wk) than treatment children (1.4 visits/wk). CONCLUSIONS: Forced use can be an effective rehabilitation technique in children with chronic hemiparesis.

Age Factors↗

Evaluation of the effects of the opioid agonist morphine on gastrointestinal tract function in horses.

OBJECTIVE: To evaluate the effects of morphine administration for 6 days on gastrointestinal tract function in healthy adult horses. ANIMALS: 5 horses. PROCEDURES: Horses were randomly allocated into 2 groups in a crossover study. Horses in the treatment group received morphine sulfate at a dosage of 0.5 mg/kg, IV, every 12 hours for 6 days. Horses in the control group received saline (0.9% NaCl) solution at a dosage of 10 mL, IV, every 12 hours for 6 days. Variables assessed included defecation frequency, weight of feces produced, intestinal transit time (evaluated by use of barium-filled spheres and radiographic detection in feces), fecal moisture content, borborygmus score, and signs of CNS excitement and colic. RESULTS: Administration of morphine resulted in gastrointestinal tract dysfunction for 6 hours after each injection. During those 6 hours, mean +/- SD defecation frequency decreased from 3.1 +/- 1 bowel movements in control horses to 0.9 +/- 0.5 bowel movements in treated horses, weight of feces decreased from 4.1 +/- 0.7 kg to 1.1 +/- 0.7 kg, fecal moisture content decreased from 76 +/- 2.7% to 73.5 +/- 2.9%, and borborygmus score decreased from 13.2 +/- 2.9 to 6.3 +/- 3.9. Mean gastrointestinal transit time was also increased, compared with transit times in control horses. CONCLUSIONS AND CLINICAL RELEVANCE: Morphine administered at 0.5 mg/kg twice daily decreased propulsive motility and moisture content in the gastrointestinal tract lumen. These effects may predispose treated horses to development of ileus and constipation.

Analgesics, Opioid↗

Characterization of mibefradil block of the human heart delayed rectifier hKv1.5.

The goal of this study was to analyze the effects of mibefradil on a human cardiac K(+) channel (hKv1.5) stably expressed in Chinese hamster ovary cells using the whole-cell configuration of the patch-clamp technique. Mibefradil inhibited in a concentration-dependent manner the hKv1.5 current with a K(D) value of 0.78 +/- 0.05 microM and a Hill coefficient of 0.97 +/- 0.06. Block induced by mibefradil was voltage dependent, consistent with a value of electrical distance of 0.13. The apparent association (k) and dissociation (l) rate constants measured at +50 mV were found to be 7.3 +/- 0.5 x 10(6) M(-1).s(-1) and 4.3 +/- 0.1 s(-1), respectively. Block increased rapidly between -20 and +10 mV, coincident with channel opening and suggested an open channel block mechanism, which was confirmed by a slower deactivation time course resulting in a "crossover" phenomenon when tail currents recorded under control conditions and in the presence of mibefradil were superimposed. Shifts toward negative potentials of the maximum conductance and the activation curve were observed, confirming the voltage dependence of block. Mibefradil induced a significant use-dependent block when trains of depolarization at frequencies between 0.02 and 2 Hz were applied. In the presence of mibefradil, recovery of inactivation was faster than under control conditions, suggesting that mibefradil might compete with the inactivation gate of hKv1.5. These results indicate that mibefradil blocks hKv1.5 channels in a concentration-, voltage-, time- and use-dependent manner and the concentrations needed to observe these effects are in the therapeutic range.

Animals↗

Oral acyclovir suppression of recurrent genital herpes: a double-blind, placebo-controlled, crossover study.

A randomised, double-blind, placebo-controlled, crossover study was conducted in 31 male patients with a history of frequently recurrent genital herpes who received consecutively 200 mg acyclovir and matching placebo by mouth four times a day for 12 weeks each. During acyclovir therapy recurrences were completely prevented in 24 (77%) and were reduced in both frequency and duration in the remainder compared with those occurring during treatment with placebo. The incidence and nature of adverse events reported during each treatment period was virtually identical. No long-term effects on recurrence rates were discernible but chronic suppressive therapy can be considered to offer the means of controlling the severe forms of disease experienced by some patients.

Acyclovir↗

[The anti-arrhythmia effect of carbamazepine in chagasic patients with advanced myocardial damage].

Oral administration of 600 mg/day of carbamazepine to 14 arrhythmic chagasic patients with advanced myocardial damage and no signs of congestive heart failure did not alter the frequency of ventricular extrasystoles, but reduced the total number of supraventricular ectopic beats in 7/14 patients and the episodes of complex ventricular arrhythmias in up to 43% of patients. This assessment was made from 24 hour continuous Holter recording during the course of this double-blind, placebo controlled, randomized crossover study. Serum levels of carbamazepine were also determined and found within therapeutic limits. Six patients complained of minor side effects. One patient presented with iatrogenic complete AV block, another case had proarrhythmic effect and one patient had to be withdrawn from the study because of gastric irritation. No instance of contractile depression was observed. Accordingly, carbamazepine is a therapeutic alternative for treatment of symptomatic complex ventricular or supraventricular arrhythmias in chronic chagasic patients without evidence of conduction system involvement or with intolerance to other antiarrhythmic drugs.

Administration, Oral↗

Efficacy of acebutolol in chronic stable angina using single-blind and randomized double-blind protocol.

The clinical effects of a cardioselective beta-adrenergic blocking drug, acebutolol, were studied in 25 patients with chronic stable angina, using a seven-week single-blind placebo leads to acebutolol (mean dose 913 mg/day) phase followed by 12-week randomized double-blind placebo leads to acebutolol (mean dose 968 mg/day) crossover protocol. Objective parameters from exercise treadmill tests showed consistent reduction in resting and maximal exercise heart rate and rate-pressure product during both single- and double-blind phases. Duration of exercise and maximal ST segment depression were not significantly altered. Subjective improvement following acebutolol was observed with reduced frequency of anginal attacks and nitroglycerin consumption during the single-blind phase. However, no differences were seen during the double-blind phase due to significant subjective improvement during the latter placebo period. Adverse effects observed were mild in nature and were similar to those seen with other beta blockers. These data establish acebutolol as a potent beta-blocking agent and emphasize the importance of utilizing objective parameters over subjective variables in demonstrating the clinical antianginal efficacy of a beta blocker.

Acebutolol↗